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SCHOOL OF SCIENCE & ENGINEERING
BACHELOR OF SCIENCE (BIOTECHNOLOGY) HONS
SEMESTER 3 / MAY 2016
COURSE CODE : SBB 2114
COURSE TITLE : DEVELOPMENTAL BIOLOGY
DEVELOPMENT OF HUMAN EMBRYO
NAME : Mohammed Ridzuwan bin Abdul Rahaman
IDENTITY CARD NO. : 1107151018
E-MEL : mohammed_rix@hotmail.com
TUTOR NAME : Mrs. Shamala Marimuthu
LEARNING CENTRE : Manipal International University Nilai
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CONTENTS PAGE
CONTENT LIST 1
1.0 INTRODUCTION 2
2.0 EMBRYONIC DEVELOPMENT
2.1 Germinal Stage 5
2.2 Gastrulation Stage 9
2.3 Neurulation Stage 12
2.4 Organogenesis Stage 13
3.0 FETAL DEVELOPMENT
3.1 Second Trimester 14
3.2 Third Trimester 14
4.0 CONCLUSION 15
REFERENCES 16
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1.0 INTRODUCTION
Human development is a continuous process that begins when an ovum is fertilized by a
sperm, a developmental process that represents an amazing integration of increasingly complex
phenomena. From a single cell to a baby in 9 months through cell division, growth, differentiation,
and even cell death, transform the fertilized ovum into a multicellular human being. The study of
these phenomena is called embryology, and the field includes investigations of the molecular, cellular,
and structural factors contributing to the formation of an organism. In the 20th century, the
embryogenesis field was blossomed. First approaches included observations of transparent embryos
from tunicates that contained pigmented cells and vital dyes were used to stain living cells to follow
their fates. In the 1960s, radioactive labels and autoradiographic techniques were employed. Later,
host embryos were examined histologically, and the fates of the quail cells were determined.
Monitoring cell fates with these and other techniques provides valuable information about the origins
of different organs and tissues (Sadler, 2012).
The human development process starts once the fertilisation occurs where the sperm cell
successfully enters and fuses with an egg cell (ovum). The genetic material of the sperm and egg then
combine to form a single cell called a zygote. In human, male gametes (haploid) called sperms are
produced in the male gonads called testes and the female gametes called ova (haploid) are produced in
the female gonads called ovaries via gametogenesis process (Embryogenesis., n.d.). There are two
types of gametogenesis: spermatogenesis which is the process of producing sperms and oogenesis
which is the process of producing ova.
Spermatogenesis Process (Figure 1.1):
Spermatogenesis, the development of sperm, is continuous and prolific (millions of sperm are
produced per day) each sperm takes about 7 weeks to develop. Primordial germ cells undergo a series
of cell division through mitosis to produce diploid spermatogonia. Each spermatogonium grows and
develop into primary spermatocyte. The primary spermatocyte than divides through meiosis to
reproduce two secondary spermatocytes at the end of meiosis I. Each secondary spermtocytes
undergoes meiosis II to form two spermatids. Each spermatids than differentiate to become a sperm.
Therefore, each spermatogonium may develop and form four sperms at the end of the sperm
formation (Marieb, 2006). In the last step, mature sperm are released into the lumen (fluid-filled
cavity) of the tubule. The sperm travel along the tubule into the epididymis, where they become
motile. Sperm cell’s head contain a haploid nucleus which is tipped with a special vesicle, the
acrosome. The acrosome contains enzymes (hydrolytic) that help the sperm penetrate an egg.
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Oogenesis Process (Figure 1.1):
In the foetal stage, the primordial germ cells divide repeatedly by mitosis to form diploid
oogonia. Each oogonium grows and develops into primary oocytes. Each primary oocytes is
surrounded by a layer of follicle cells to form a primary follicle. At birth, the ovary of baby girl has
millions of primary oocytes. After birth, the primary oocytes undergo meiosis I but stop at prophase I
until puberity. At puberity, one primary oocyte completes meiosis I to form two haploid cells: a
secondary oocyte and a polar body. The secondary oocyte is larger than the polar body because of the
unequal division of cytoplast. The secondary oocyte is surrounded by follicle cells and known as a
secondary follicle. The secondary follicle develops and matures to form a Graafian follicle. The
Graafian follicle than moves to the site of the ovarian wall. During ovulation, the Graafian follicle
bursts and releases the secondary oocyte from the ovary into the Fallopian tube (Betsy, 2009).
Figure 1.1: Gametogenesis Diagram (Oogenesis & Spermatogenesis)
Source: https://s-media-cache-ak0.pinimg.com/736x/6a/76/f6/6a76f65cef9ade43c1bebb71a2.jpg
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The development of human before birth divided into two: embryonic development which is
from 1st
week until 8th
week (known as first trimester) and fetal development from 9th
week until 37th
week (known as second and third trimester). Embryonic period is also considered the organogenic
period, when most organs within the embryo have begun to form. While fetal period (4x the
embryonic period) is a time of extensive growth in size and mass as well as ongoing differentiation of
organ systems established in the embryonic period (Hill, 2015). There are several stages in embryonic
development which is germinal, gastrulation, neurulation and organogenesis stage. Germinal stage
involves fertilization, cleavage and blastulation processes. Fertilization takes place when the sperm
has successfully entered the ovum and the two sets of genetic material carried by the gametes, fuse
together, resulting in the zygote, (a single diploid cell). Cleavage process is marked when the zygote
divides through mitosis into two cells then continues into four cells, eight cells and so on. Cleavage
itself is the first stage in blastulation, the process of forming the blastocyst. Cells differentiate into an
outer layer of cells (collectively called the trophoblast) and an inner cell mass. The process of
gastrulation reorganises the two-layer embryo into a three-layer embryo which is ectoderm, mesoderm
and endoderm. Following gastrulation, the ectoderm gives rise to epithelial and neural tissue, and
transformed into the neural tube which is known as neurulation process (Shamala, 2016). Lastly,
organogenesis where many different systems formed, grow and differentiate further during the fetal
period and do so at different times.
Fetal development clinically described as the Second Trimester and Third Trimester. Many of
the critical measurements of growth are now carried out by ultrasound and this period ends at birth.
For example, the brain continues to grow and develop extensively during this period (and postnatally),
the respiratory system differentiates (and completes only just before birth), the urogenital system
further differentiates between male/female, endocrine and gastrointestinal tract begins to function.
Also consider the systems (respiratory, cardiac, neural) that will still not have their final organization
and function determined until after birth (Hill, 2015).
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2.0 EMBRYONIC DEVELOPMENT
The process of progressing from a single cell through the period of establishing organ
primordia (the first 8 weeks of human development) is called the period of embryogenesis. Human
embryonic development drived by cell division and cellular differentiation of the embryo that occurs
at first eight weeks after fertilization until it become a fetus. The staging of human embryos was
introduced in 1914 by Franklin P. Mall at the Department of Embryology of the Carnegie Institution
of Washington. Mall's sucessor, George L. Streeter, later refined the classification of human embryos
into 23 stages, or "developmental horizons" (Louisiana State University Health Sciences Center New
Orleans [LSUHSC], 2012). Embryonic development can be divided into different developmental
phases but there are four main stages should considered, which are germinal, gastrulation, neurulation
and organogenesis stages.
2.1 Germinal Stage:
The germinal stage is the prenatal, developmental stage that begins at conception and lasts
through the second week of pregnancy. During this time, the fertilized egg makes it way down the
fallopian tube, and begins to have cell reproduction. Eventually, the single celled zygote becomes a
multi celled ball that attaches itself to the wall of the uterus around the end of the second week, which
constitutes the beginning of the embryonic stage (Embryogenesis., n.d.). Germinal stage involves
fertilization, cleavage and blastulation processes.
i. Fertilization (Figure 2.1 a):
Fertilization is the formation of a diploid zygote from a haploid egg and sperm (1st
day).
Sperm penetrate the protective layer around the egg by ezymatic reaction. Receptors on the
egg surface bind to molecules on the sperm surface. Changes at the egg surface prevent
polyspermy, the entry of multiple sperm nuclei into the egg. The acrosomal reaction is
triggered when the sperm meets the egg. The acrosome at the tip of the sperm releases
hydrolytic enzymes that digest material surrounding the egg. Gamete contact and/or fusion
depolarizes the egg cell membrane and sets up a fast block to polyspermy. Fusion of egg and
sperm also initiates the cortical reaction. Seconds after the sperm binds to the egg, vesicles
just beneath the egg plasma membrane release their contents and form a fertilization
envelope. The fertilization envelope acts as the slow block to polyspermy. The cortical
reaction requires a high concentration of Ca22+
ions in the egg. The reaction is triggered by a
change in Ca2+
concentration. Ca2+
spread across the egg correlates with the appearance of
the fertilization envelope (Pratheep, 2015).
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Figure 2.1 (a): Fertilzation (Acrosomal & Cortical Reaction)
Source: http://bio1152.nicerweb.com/Locked/media/ch47/47_3AcrosomalCorticalRxn_L.jpg
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ii. Cleavage (Figure 2.1 b):
As a result of fertilization, cleavage is initiated through rapid mitotic divison of zygote.
From this moment on, the zygote will develop, first two cells divide into four cells, then into
eight cells and so on. These number of daughter cells are called blastomeres. Each division
takes from 12 to 24 hours (2nd
- 3rd
day). Characteristic for this process is the fact that during
cleavage each new cell (blastomere) contains half the volume of cytoplasm of the mother
cell. This process will go on until a specific ratio is reached between the cell volume and the
volume of the nucleus: the volumetric ratio between nucleus and the cytoplasm has gained a
value characteristic of the human organism in question. The amount of cytoplasm of the
zygote is so large that this does not take place till the zygote reaches the 16-cell stage
(morula). At this stage the cells start to bind firmly together in a process called compaction,
and cleavage continues as cellular differentiation. During the process of cleavage the overall
size of the zygote does not change (Guus, 2011).
Figure 2.1 (b): Human Embryo Cleavage
Source: http://media.buzzle.com/media/images-en/illustrations/human-biology/1200-46482592-
human-embryo-development.jpg
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iii. Blastulation (Figure 2.1 c):
After fertilization (5th
– 6th
day), the formed cluster of blastomeres (morula), undergoes the
process of compaction which the embryo transforms into a blastocyst. In compaction the
peripheral cells begin to stick together in much closer contact than before, forming a more
dense structure. It is a process comparable to epithelialisation. These peripheral cells will give
rise to the trophoblast. The trophoblast cells secrete a fluid into the central cavity - the
blastocyst cavity or blastocoel - lining the cavity. The inner cells move toward one pole,
forming the inner cell mass (ICM). These cells maintain their pluripotent state and will form
the embryo proper, while the trophectoderm cells will give rise to the embryonic placenta.
The blastocoel continues to gradually increase its volume and the blastocyst expands. The
zona pellucida is still present, but its components will be soon lysed by a blastocyst-secreted
protease, known as strypsin, and by proteolytic enzymes produced by the endometrium
(Brevini & Pennarossa, 2013). The process that leads to zona pellucida degradation is
described as hatching and enable the trophoblast cells to directly bind the uterine cavity which
is implantation.
Figure 2.1 (c): Human Embryo Blastulation
Source: http://previews.123rf.com/images/designua/des1510/designua151000012/47088842-
blastocyst-Human-blastocyst-with-inner-cell-mass-the-mammalian-conceptus-in-the-post-
morula-stage-co-Stock-Vector.jpg
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2.2 Gastrulation Stage:
The formation of epiblast and hypoblast, movement and rearangement of blastomeres by
changes of their position relative to one another is called gastrulation and also extension of
extraembryonic membrane by outer layer of embryo (trophoblast). Involves changes in cell motility,
cell shape, and cell adhesion. By the end of gastrulation, the cells of the embryo must rearranged into
three primary germ layers: ectoderm, mesoderm, and endoderm.
i. Formation Of Epiblast And Hypoblast (Figure 2.2 a):
Once cleavage has resulted in the multi-celled blastocyst, morphogenetic movements will
come into play to reorganize the embryo into distinct layers and will have different
developmental fates. Then, new relationships appear between different groups of cells taht
allow new inter-cellular communications. Inner Cell Mass (ICM) delaminates to form
hypoblast and epiblast. Epiblast is 2-layered disc of approximately cuboidal cells & will
form the embryo proper. Flatter hypoblast cells lie below the epiblast and form yolk sac
(Raven & Johnson, 2001).
Figure 2.2 (a): Formation Of Epiblast And Hypoblast
Source: http://www.utm.utoronto.ca/~w3bio380/pdf/OLD-PDF/2010%20Summer/Gastrul
ation.pdf
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ii. Movement And Rearangement Of Blastomeres (Figure 2.2 b):
1. Ingression - cells break away from the tissue and migrate as individuals:
epithelial-mesenchymal transition,
2. Delamination - layers of cells separate from each others more or less as sheets
of cells: formation of the epiblast/hypoblast,
3. Intercalate - two cell layers interlace with each other,
4. Epiboly - a form of cell spreading in which cells flatten out; this allows them to
cover a much larger surface area of epiblast,
5. Invaginate - a tissue layer folds in (out); optic (eye) vesicle formation,
6. Involute - cells move over a lip of tissue and into the interior, and
7. Convergent Extension - cells reorganize to form less layers allowing the cells to
extend out from a point; formation of the chordamesoderm: notochordal process.
Figure 2.2 (b): Cell Movements & Rearrangements During Embryonic Development
Source: http://www.utm.utoronto.ca/~w3bio380/pdf/OLD-PDF/2010%20Summer/Gastrul
ation.pdf
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iii. Formation Of Primary Germ Layer (Figure 2.2 c):
The primitive streak, a linear band of cells formed by the migrating epiblast, appears, and
this marks the beginning of gastrulation, which takes place around the sixteenth day (week
3). Initially cells move along surface but upon reaching the center line (primitive streak)
will enter the embryo, turn the corner and move internally. The moving surface cells first
pile up to form primitive node. This occurs because the cells move along the top faster
than they can separate off and move internally. The cells that enter through the primitive
node will become the notochord which lies directly underneath (Danton, 2010). The
epiblast has now differentiated from two germ layer into the three germ layers of the
embryo, so that the bilaminar disc is now a trilaminar disc, the gastrula.
1. The ectoderm - which will develop into the skin and nervous system;
2. The mesoderm - which will develop into muscles, skeleton, connective tissue,
blood, gonads, and kidneys;
3. The endoderm - which will develop into the lining of the gut tube and
respiratory system.
Figure 2.2 (c): Tissue Formation
Source: http://www.utm.utoronto.ca/~w3bio380/pdf/OLD-PDF/2010%20Summer/Gastrul
ation.pdf
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iv. Extraembryonic Membranes (Figure 2.2 d):
The embryo membrane and trophoblast form from embryonic cells located outside of the
body of the embryo known as extraembryonic membranes. The extraembryonic
membranes, later to become the fetal membranes, include the amnion, placenta, and
umblical cord. The trophoblast implants into the endometrial lining of its mother’s uterus
and becomes the chorionic membrane. The part of the chorion in contact with endometrial
tissue contributes to the placenta. The allantois in contributes blood vessels to the structure
that will become the umbilical cord, so that fetal blood can be delivered to the placenta for
gas exchange (Raven & Johnson, 2001).
Figure 2.2 (d): Extraembryonic Membranes
Source: www.mhhe.com/biosci/genbio/raven6b/graphics/raven06b/other/raven06_60.pdf
2.3 Neurulation Stage (Figure 2.3):
After the gastrulation stage, the three primary cell layers undergoes transformation and
differentiation, where the notochord and the hollow dorsal nerve cord form. This development of the
dorsal nerve cord is called neurulation. The notochord is first visible soon after gastrulation is
complete, a layer of ectodermal cells situated above the notochord invaginates, forming from
mesoderm along the dorsal midline, the neural groove of the embryo. By the end of the third week,
the lateral edge of the neural plate become elevated to form neural folds, and the depressed midregion
forms the neural groove. Gradually, the neural folds move towards each other in the midline and fuse,
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creating a long hollow cylinder (neural tube). Until fusion is complete, the cephalic and caudal ends
of the neural tube communicate with the amniotic cavity by way of the anterior (cranial) and posterior
(caudal) neuropores, respectively. Closure of the cranial neuropore occurs at approximately day 25,
whereas the posterior neuropore closes at day 28. Neurulation is then complete, and the central
nervous system is represented by a closed tubular structure with a narrow caudal portion, the spinal
cord, and a much broader cephalic portion characterized by a number of dilations, the brain vesicles
(Taube, n.d.).
Figure 2.3: Neurulation
Source: http://www.apsubiology.org/anatomy/2020_Exam_Reviews/_5/28-09cd_Neurulation_1.jpg
2.4 Organogenesis Stage:
Is the process by which the ectoderm, endoderm, and mesoderm develop into the internal
organs of the organism. This process takes place between about week 3 to the end of week 8. At the
end of this period the embryo is referred to as a fetus.. The germ layers in organogenesis differ by
three processes: folds, splits, and condensation. By week five, the buds of tissue which will become
the limbs are in place. The structures which will become the skeleton, nervous system, and circulatory
system of the face, neck, and jaws are in place. A five-week-old embryo has the early developmental
structures of the esophagus, stomach, intestine, liver, and pancreas. The heart is already functioning,
and continues to develop and change over this period of time. The respiratory system begins
developing, as do blood vessels, blood cells, nervous and endocrine organs. Clearly, the most crucial
organs of the human form are developing during organogenesis (Gajaan & Tossif, 2013).
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3.0 FETAL DEVELOPMENT
After the 8 week of embryonic development, the developing organism is called a fetus (fetal
development. All major structures are already formed in the fetus, but they continue to grow and
develop. Since the precursors of all the major organs are created by this time, the fetal period is
described both by organ and by a list of changes by weeks of gestational age. This development
divided into 2 main stages: second trimester (3 months) and third trimester (4 months).
3.1 Second Trimester:
During the second trimester (the next three months of pregnancy) the bones actively enlarge
and the brain develops a lot. During the second trimester until about 24 weeks, the fetus cannot live
outside of the body because its lungs, heart and blood systems have not developed enough. The face
looks more human, the baby has hair, the ears stand out, and the baby can hear the mother’s voice.
Between 16 and 20 weeks, the baby’s movements may be felt. The baby begins to store some
antibodies and this slowly increases until birth. Eyebrows and eyelashes appear. A fine downy hair
(lanugo) appears all over the baby’s body (BC Ministry of Health [BCMOH], 2011). The baby’s skin
is thin, shiny, and covered with a creamy protective coating called vernix. The baby’s legs lengthen,
and move well. Teeth develop-enamel and dentine are being formed. By the end of the fifth month the
baby is about half the length of a newborn. During the second trimester, meconium (the baby’s first
stool) begins to appear in the intestines. The fetus has grown to about 175 millimeters in length and
attained a weight of about 225 grams (Raven & Johnson, 2001).
3.2 Third Trimester:
During the third trimester (the last 3 months of pregnancy is predominantly a period of growth
rather than development. The weight of the fetus doubles several times, but this increase in bulk is not
the only kind of growth that occurs. Most of the major nerve tracts in the brain, as well as many new
neurons (nerve cells), are formed during this period. By week 28 the fetus can now store iron,
calcium, and other nutrients and the fetus can hear and respond to sounds. After week 32 the male
fetus’s testicles begin to drop into the scrotum and the pupils in the fetus’s eyes can react to light
(BCMOH, 2011). Neurological growth is far from complete at the end of the third trimester, when
birth takes place. The downy hair on the fetus’s body begins to disappear by week 36. The baby
continues to increase the store of antibodies and is able to resist some diseases. The testicles of male
fetus are now in the scrotum and the labia majora of female fetus are developed. The fetus is now full
term at week 40. The lungs of fetus completly grown and the fetus starts to breath and try to come out
from mother’s uterus (Meeks, 1982).
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4.0 CONCLUSION
From a single cell to a baby in 9 months; a developmental process that represents an amazing
integration of increasingly complex phenomena. The study of these phenomena is called embryology,
and the field includes investigations of the molecular, cellular, and structural factors contributing to
the formation of an organism. These studies are important because they provide knowledge essential
for creating health care strategies for better reproductive outcomes. Thus, our increasingly better
understanding of embryology has resulted in new techniques for prenatal diagnoses and treatments,
therapeutic procedures to circumvent problems with infertility, and mechanisms to prevent birth
defects, the leading cause of infant mortality. These improvements in prenatal and reproductive health
care are significant not only for their contributions to improved birth outcomes but also for their long-
term effects postnatally. The development of human before birth divided into two: embryonic
development which is from 1st
week until 8th
week (known as first trimester) and fetal development
from 9th
week until 37th
week (known as second and third trimester). Embryonic period is also
considered the organogenic period, when most organs within the embryo have begun to form. While
fetal period is a time of extensive growth in size and mass as well as ongoing differentiation of organ
systems established in the embryonic period. There are several stages in embryonic development
which is germinal, gastrulation, neurulation and organogenesis stage. Germinal stage involves
fertilization, cleavage and blastulation processes. While gastrulation stage involves formation of
epiblast and hypoblast, movement and rearangement of blastomeres by changes of their position
relative to one another and also extension of extraembryonic membrane by trophoblast, the cells of
the embryo rearranged into three primary germ layers: ectoderm, mesoderm, and endoderm. After the
gastrulation stage, neurulation stage occur, where the three primary cell layers undergoes
transformation and differentiation to form the notochord and the hollow dorsal nerve cord. Lastly in
embryonic development the organogenesis stage takes place, by which the ectoderm, endoderm, and
mesoderm develop into the internal organs of the organism within week 3 to the end of week 8. After
the 8 week of embryonic development, the fetal development will start. This development mainly for
growing and development of organs. Fetus development divided into 2 main stages: second trimester
(3 months) and third trimester (4 months). The critical stages of human development take place quite
early, and the following six months are essentially a period of growth. The growth of the brain is not
yet complete, however, by the end of the third trimester, and must be completed postnatally.
(Total Words = 3500)
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REFERENCES
BC Ministry of Health, [BCMOH]. (2011). The best chance: Stages of pregnancy. Retrieved from:
http://www.bestchance.gov.bc.ca/pregnancy/2nd-trimester/stages-of-pregnancy/3rd-trimester-
baby.html.
Betsy, T.L.H. (2009). Longman Essential Revision Guide for Exam Success Biology. Malaysia:
Pearson Sdn. Bhd.
Brevini, T.A.L., & Pennarossa, G. (2013). Gametogenesis, Early Embryo Development, and Stem Cell
Derivation, SpringerBriefs in Stem Cells. DOI: 10.1007/978-1-4614-5532-5_2.
Danton, H.(2010). Gastrulation: formation of the primary germ layers [PDF document]. Retrieved
fromhttp://www.utm.utoronto.ca/~w3bio380/pdf/OLD-PDF/2010%20Summer/Gastrulation.pdf
Embryogenesis. (n.d.). In Wikipedia. Retrieved May 20, 2016, from
https://en.wikipedia.org/wiki/Embryogenesis
Gajaan, S., & Tossif, G. (2013). Organogenesis Critical period of Organogenesis [PowerPoint slides].
Retrieved from www.slideshare.net/applevsamsung/organogenesis.
Guus, V.D.B. (2011). Embryology: Early development from a phenomenological point of view.
Netherlands: Bolk’s Companions. Retrieved from
http://www.louisbolk.org/downloads/1281.pdf.
Hill, M.A. (2015, November 16). Embryology Embryonic Development. UNSW Embryology
[mediawiki]. Retrieved June 3, 2016, from
https://embryology.med.unsw.edu.au/embryology/index.php/Embryonic_Development
Louisiana State University Health Sciences Center New Orleans [LSUHSC]. (2012, November 30).
The Stages of Human Embryonic Development. Virtual Human Embryo Project
[www.ehd.org]. Retrieved from
http://virtualhumanembryo.lsuhsc.edu/DREM/Contact_info_EHD.html.
Marieb, E.N. (2006). Essential of Human Anatomy & Physiology. 8th ed. Addison Wesley Longman.
Meeks, J. (1982). Family Living and Human Reproduction. Columbus, OH: Charles E. Merrill Pub.
Co. Retrieved from http://www.edu.gov.mb.ca/k12/cur/physhlth/hs_k-8/blms/blm7-1-1.pdf.
Pratheep, S. (2015). Chapter 4: General embryology- Animal [PowerPoint slides]. Lecture Notes.
Raven, P.H., & Johnson, G.B. (2001). Biology: 6th edition. Retrieved from
www.mhhe.com/biosci/genbio/raven6b/graphics/raven06b/other/raven06_60.pdf
Sadler, T.W. (2012). Medical Embryology, 12th edition. Retrieved from
http://medfile.ir/iran%20anatomy%20files/text/Langman's%20Medical%20Embryology%2012t
h%20Edition%20(www.irananatomy.ir).pdf.
Shamala, M.(2016). Developmental Biology: Chapter 1 [PowerPoint slides]. Lecture Notes.
Taube, P.R.(n.d.). Ectoderm: Neurulation, Neural Tube, Neural Crest [PDF document]. Retrieved
from http://www.columbia.edu/itc/hs/medical/humandev/2004/Chapt4-Ectoderm.pdf.

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Developmental biology

  • 1. SCHOOL OF SCIENCE & ENGINEERING BACHELOR OF SCIENCE (BIOTECHNOLOGY) HONS SEMESTER 3 / MAY 2016 COURSE CODE : SBB 2114 COURSE TITLE : DEVELOPMENTAL BIOLOGY DEVELOPMENT OF HUMAN EMBRYO NAME : Mohammed Ridzuwan bin Abdul Rahaman IDENTITY CARD NO. : 1107151018 E-MEL : mohammed_rix@hotmail.com TUTOR NAME : Mrs. Shamala Marimuthu LEARNING CENTRE : Manipal International University Nilai
  • 2. SBB 2114 1 CONTENTS PAGE CONTENT LIST 1 1.0 INTRODUCTION 2 2.0 EMBRYONIC DEVELOPMENT 2.1 Germinal Stage 5 2.2 Gastrulation Stage 9 2.3 Neurulation Stage 12 2.4 Organogenesis Stage 13 3.0 FETAL DEVELOPMENT 3.1 Second Trimester 14 3.2 Third Trimester 14 4.0 CONCLUSION 15 REFERENCES 16
  • 3. SBB 2114 2 1.0 INTRODUCTION Human development is a continuous process that begins when an ovum is fertilized by a sperm, a developmental process that represents an amazing integration of increasingly complex phenomena. From a single cell to a baby in 9 months through cell division, growth, differentiation, and even cell death, transform the fertilized ovum into a multicellular human being. The study of these phenomena is called embryology, and the field includes investigations of the molecular, cellular, and structural factors contributing to the formation of an organism. In the 20th century, the embryogenesis field was blossomed. First approaches included observations of transparent embryos from tunicates that contained pigmented cells and vital dyes were used to stain living cells to follow their fates. In the 1960s, radioactive labels and autoradiographic techniques were employed. Later, host embryos were examined histologically, and the fates of the quail cells were determined. Monitoring cell fates with these and other techniques provides valuable information about the origins of different organs and tissues (Sadler, 2012). The human development process starts once the fertilisation occurs where the sperm cell successfully enters and fuses with an egg cell (ovum). The genetic material of the sperm and egg then combine to form a single cell called a zygote. In human, male gametes (haploid) called sperms are produced in the male gonads called testes and the female gametes called ova (haploid) are produced in the female gonads called ovaries via gametogenesis process (Embryogenesis., n.d.). There are two types of gametogenesis: spermatogenesis which is the process of producing sperms and oogenesis which is the process of producing ova. Spermatogenesis Process (Figure 1.1): Spermatogenesis, the development of sperm, is continuous and prolific (millions of sperm are produced per day) each sperm takes about 7 weeks to develop. Primordial germ cells undergo a series of cell division through mitosis to produce diploid spermatogonia. Each spermatogonium grows and develop into primary spermatocyte. The primary spermatocyte than divides through meiosis to reproduce two secondary spermatocytes at the end of meiosis I. Each secondary spermtocytes undergoes meiosis II to form two spermatids. Each spermatids than differentiate to become a sperm. Therefore, each spermatogonium may develop and form four sperms at the end of the sperm formation (Marieb, 2006). In the last step, mature sperm are released into the lumen (fluid-filled cavity) of the tubule. The sperm travel along the tubule into the epididymis, where they become motile. Sperm cell’s head contain a haploid nucleus which is tipped with a special vesicle, the acrosome. The acrosome contains enzymes (hydrolytic) that help the sperm penetrate an egg.
  • 4. SBB 2114 3 Oogenesis Process (Figure 1.1): In the foetal stage, the primordial germ cells divide repeatedly by mitosis to form diploid oogonia. Each oogonium grows and develops into primary oocytes. Each primary oocytes is surrounded by a layer of follicle cells to form a primary follicle. At birth, the ovary of baby girl has millions of primary oocytes. After birth, the primary oocytes undergo meiosis I but stop at prophase I until puberity. At puberity, one primary oocyte completes meiosis I to form two haploid cells: a secondary oocyte and a polar body. The secondary oocyte is larger than the polar body because of the unequal division of cytoplast. The secondary oocyte is surrounded by follicle cells and known as a secondary follicle. The secondary follicle develops and matures to form a Graafian follicle. The Graafian follicle than moves to the site of the ovarian wall. During ovulation, the Graafian follicle bursts and releases the secondary oocyte from the ovary into the Fallopian tube (Betsy, 2009). Figure 1.1: Gametogenesis Diagram (Oogenesis & Spermatogenesis) Source: https://s-media-cache-ak0.pinimg.com/736x/6a/76/f6/6a76f65cef9ade43c1bebb71a2.jpg
  • 5. SBB 2114 4 The development of human before birth divided into two: embryonic development which is from 1st week until 8th week (known as first trimester) and fetal development from 9th week until 37th week (known as second and third trimester). Embryonic period is also considered the organogenic period, when most organs within the embryo have begun to form. While fetal period (4x the embryonic period) is a time of extensive growth in size and mass as well as ongoing differentiation of organ systems established in the embryonic period (Hill, 2015). There are several stages in embryonic development which is germinal, gastrulation, neurulation and organogenesis stage. Germinal stage involves fertilization, cleavage and blastulation processes. Fertilization takes place when the sperm has successfully entered the ovum and the two sets of genetic material carried by the gametes, fuse together, resulting in the zygote, (a single diploid cell). Cleavage process is marked when the zygote divides through mitosis into two cells then continues into four cells, eight cells and so on. Cleavage itself is the first stage in blastulation, the process of forming the blastocyst. Cells differentiate into an outer layer of cells (collectively called the trophoblast) and an inner cell mass. The process of gastrulation reorganises the two-layer embryo into a three-layer embryo which is ectoderm, mesoderm and endoderm. Following gastrulation, the ectoderm gives rise to epithelial and neural tissue, and transformed into the neural tube which is known as neurulation process (Shamala, 2016). Lastly, organogenesis where many different systems formed, grow and differentiate further during the fetal period and do so at different times. Fetal development clinically described as the Second Trimester and Third Trimester. Many of the critical measurements of growth are now carried out by ultrasound and this period ends at birth. For example, the brain continues to grow and develop extensively during this period (and postnatally), the respiratory system differentiates (and completes only just before birth), the urogenital system further differentiates between male/female, endocrine and gastrointestinal tract begins to function. Also consider the systems (respiratory, cardiac, neural) that will still not have their final organization and function determined until after birth (Hill, 2015).
  • 6. SBB 2114 5 2.0 EMBRYONIC DEVELOPMENT The process of progressing from a single cell through the period of establishing organ primordia (the first 8 weeks of human development) is called the period of embryogenesis. Human embryonic development drived by cell division and cellular differentiation of the embryo that occurs at first eight weeks after fertilization until it become a fetus. The staging of human embryos was introduced in 1914 by Franklin P. Mall at the Department of Embryology of the Carnegie Institution of Washington. Mall's sucessor, George L. Streeter, later refined the classification of human embryos into 23 stages, or "developmental horizons" (Louisiana State University Health Sciences Center New Orleans [LSUHSC], 2012). Embryonic development can be divided into different developmental phases but there are four main stages should considered, which are germinal, gastrulation, neurulation and organogenesis stages. 2.1 Germinal Stage: The germinal stage is the prenatal, developmental stage that begins at conception and lasts through the second week of pregnancy. During this time, the fertilized egg makes it way down the fallopian tube, and begins to have cell reproduction. Eventually, the single celled zygote becomes a multi celled ball that attaches itself to the wall of the uterus around the end of the second week, which constitutes the beginning of the embryonic stage (Embryogenesis., n.d.). Germinal stage involves fertilization, cleavage and blastulation processes. i. Fertilization (Figure 2.1 a): Fertilization is the formation of a diploid zygote from a haploid egg and sperm (1st day). Sperm penetrate the protective layer around the egg by ezymatic reaction. Receptors on the egg surface bind to molecules on the sperm surface. Changes at the egg surface prevent polyspermy, the entry of multiple sperm nuclei into the egg. The acrosomal reaction is triggered when the sperm meets the egg. The acrosome at the tip of the sperm releases hydrolytic enzymes that digest material surrounding the egg. Gamete contact and/or fusion depolarizes the egg cell membrane and sets up a fast block to polyspermy. Fusion of egg and sperm also initiates the cortical reaction. Seconds after the sperm binds to the egg, vesicles just beneath the egg plasma membrane release their contents and form a fertilization envelope. The fertilization envelope acts as the slow block to polyspermy. The cortical reaction requires a high concentration of Ca22+ ions in the egg. The reaction is triggered by a change in Ca2+ concentration. Ca2+ spread across the egg correlates with the appearance of the fertilization envelope (Pratheep, 2015).
  • 7. SBB 2114 6 Figure 2.1 (a): Fertilzation (Acrosomal & Cortical Reaction) Source: http://bio1152.nicerweb.com/Locked/media/ch47/47_3AcrosomalCorticalRxn_L.jpg
  • 8. SBB 2114 7 ii. Cleavage (Figure 2.1 b): As a result of fertilization, cleavage is initiated through rapid mitotic divison of zygote. From this moment on, the zygote will develop, first two cells divide into four cells, then into eight cells and so on. These number of daughter cells are called blastomeres. Each division takes from 12 to 24 hours (2nd - 3rd day). Characteristic for this process is the fact that during cleavage each new cell (blastomere) contains half the volume of cytoplasm of the mother cell. This process will go on until a specific ratio is reached between the cell volume and the volume of the nucleus: the volumetric ratio between nucleus and the cytoplasm has gained a value characteristic of the human organism in question. The amount of cytoplasm of the zygote is so large that this does not take place till the zygote reaches the 16-cell stage (morula). At this stage the cells start to bind firmly together in a process called compaction, and cleavage continues as cellular differentiation. During the process of cleavage the overall size of the zygote does not change (Guus, 2011). Figure 2.1 (b): Human Embryo Cleavage Source: http://media.buzzle.com/media/images-en/illustrations/human-biology/1200-46482592- human-embryo-development.jpg
  • 9. SBB 2114 8 iii. Blastulation (Figure 2.1 c): After fertilization (5th – 6th day), the formed cluster of blastomeres (morula), undergoes the process of compaction which the embryo transforms into a blastocyst. In compaction the peripheral cells begin to stick together in much closer contact than before, forming a more dense structure. It is a process comparable to epithelialisation. These peripheral cells will give rise to the trophoblast. The trophoblast cells secrete a fluid into the central cavity - the blastocyst cavity or blastocoel - lining the cavity. The inner cells move toward one pole, forming the inner cell mass (ICM). These cells maintain their pluripotent state and will form the embryo proper, while the trophectoderm cells will give rise to the embryonic placenta. The blastocoel continues to gradually increase its volume and the blastocyst expands. The zona pellucida is still present, but its components will be soon lysed by a blastocyst-secreted protease, known as strypsin, and by proteolytic enzymes produced by the endometrium (Brevini & Pennarossa, 2013). The process that leads to zona pellucida degradation is described as hatching and enable the trophoblast cells to directly bind the uterine cavity which is implantation. Figure 2.1 (c): Human Embryo Blastulation Source: http://previews.123rf.com/images/designua/des1510/designua151000012/47088842- blastocyst-Human-blastocyst-with-inner-cell-mass-the-mammalian-conceptus-in-the-post- morula-stage-co-Stock-Vector.jpg
  • 10. SBB 2114 9 2.2 Gastrulation Stage: The formation of epiblast and hypoblast, movement and rearangement of blastomeres by changes of their position relative to one another is called gastrulation and also extension of extraembryonic membrane by outer layer of embryo (trophoblast). Involves changes in cell motility, cell shape, and cell adhesion. By the end of gastrulation, the cells of the embryo must rearranged into three primary germ layers: ectoderm, mesoderm, and endoderm. i. Formation Of Epiblast And Hypoblast (Figure 2.2 a): Once cleavage has resulted in the multi-celled blastocyst, morphogenetic movements will come into play to reorganize the embryo into distinct layers and will have different developmental fates. Then, new relationships appear between different groups of cells taht allow new inter-cellular communications. Inner Cell Mass (ICM) delaminates to form hypoblast and epiblast. Epiblast is 2-layered disc of approximately cuboidal cells & will form the embryo proper. Flatter hypoblast cells lie below the epiblast and form yolk sac (Raven & Johnson, 2001). Figure 2.2 (a): Formation Of Epiblast And Hypoblast Source: http://www.utm.utoronto.ca/~w3bio380/pdf/OLD-PDF/2010%20Summer/Gastrul ation.pdf
  • 11. SBB 2114 10 ii. Movement And Rearangement Of Blastomeres (Figure 2.2 b): 1. Ingression - cells break away from the tissue and migrate as individuals: epithelial-mesenchymal transition, 2. Delamination - layers of cells separate from each others more or less as sheets of cells: formation of the epiblast/hypoblast, 3. Intercalate - two cell layers interlace with each other, 4. Epiboly - a form of cell spreading in which cells flatten out; this allows them to cover a much larger surface area of epiblast, 5. Invaginate - a tissue layer folds in (out); optic (eye) vesicle formation, 6. Involute - cells move over a lip of tissue and into the interior, and 7. Convergent Extension - cells reorganize to form less layers allowing the cells to extend out from a point; formation of the chordamesoderm: notochordal process. Figure 2.2 (b): Cell Movements & Rearrangements During Embryonic Development Source: http://www.utm.utoronto.ca/~w3bio380/pdf/OLD-PDF/2010%20Summer/Gastrul ation.pdf
  • 12. SBB 2114 11 iii. Formation Of Primary Germ Layer (Figure 2.2 c): The primitive streak, a linear band of cells formed by the migrating epiblast, appears, and this marks the beginning of gastrulation, which takes place around the sixteenth day (week 3). Initially cells move along surface but upon reaching the center line (primitive streak) will enter the embryo, turn the corner and move internally. The moving surface cells first pile up to form primitive node. This occurs because the cells move along the top faster than they can separate off and move internally. The cells that enter through the primitive node will become the notochord which lies directly underneath (Danton, 2010). The epiblast has now differentiated from two germ layer into the three germ layers of the embryo, so that the bilaminar disc is now a trilaminar disc, the gastrula. 1. The ectoderm - which will develop into the skin and nervous system; 2. The mesoderm - which will develop into muscles, skeleton, connective tissue, blood, gonads, and kidneys; 3. The endoderm - which will develop into the lining of the gut tube and respiratory system. Figure 2.2 (c): Tissue Formation Source: http://www.utm.utoronto.ca/~w3bio380/pdf/OLD-PDF/2010%20Summer/Gastrul ation.pdf
  • 13. SBB 2114 12 iv. Extraembryonic Membranes (Figure 2.2 d): The embryo membrane and trophoblast form from embryonic cells located outside of the body of the embryo known as extraembryonic membranes. The extraembryonic membranes, later to become the fetal membranes, include the amnion, placenta, and umblical cord. The trophoblast implants into the endometrial lining of its mother’s uterus and becomes the chorionic membrane. The part of the chorion in contact with endometrial tissue contributes to the placenta. The allantois in contributes blood vessels to the structure that will become the umbilical cord, so that fetal blood can be delivered to the placenta for gas exchange (Raven & Johnson, 2001). Figure 2.2 (d): Extraembryonic Membranes Source: www.mhhe.com/biosci/genbio/raven6b/graphics/raven06b/other/raven06_60.pdf 2.3 Neurulation Stage (Figure 2.3): After the gastrulation stage, the three primary cell layers undergoes transformation and differentiation, where the notochord and the hollow dorsal nerve cord form. This development of the dorsal nerve cord is called neurulation. The notochord is first visible soon after gastrulation is complete, a layer of ectodermal cells situated above the notochord invaginates, forming from mesoderm along the dorsal midline, the neural groove of the embryo. By the end of the third week, the lateral edge of the neural plate become elevated to form neural folds, and the depressed midregion forms the neural groove. Gradually, the neural folds move towards each other in the midline and fuse,
  • 14. SBB 2114 13 creating a long hollow cylinder (neural tube). Until fusion is complete, the cephalic and caudal ends of the neural tube communicate with the amniotic cavity by way of the anterior (cranial) and posterior (caudal) neuropores, respectively. Closure of the cranial neuropore occurs at approximately day 25, whereas the posterior neuropore closes at day 28. Neurulation is then complete, and the central nervous system is represented by a closed tubular structure with a narrow caudal portion, the spinal cord, and a much broader cephalic portion characterized by a number of dilations, the brain vesicles (Taube, n.d.). Figure 2.3: Neurulation Source: http://www.apsubiology.org/anatomy/2020_Exam_Reviews/_5/28-09cd_Neurulation_1.jpg 2.4 Organogenesis Stage: Is the process by which the ectoderm, endoderm, and mesoderm develop into the internal organs of the organism. This process takes place between about week 3 to the end of week 8. At the end of this period the embryo is referred to as a fetus.. The germ layers in organogenesis differ by three processes: folds, splits, and condensation. By week five, the buds of tissue which will become the limbs are in place. The structures which will become the skeleton, nervous system, and circulatory system of the face, neck, and jaws are in place. A five-week-old embryo has the early developmental structures of the esophagus, stomach, intestine, liver, and pancreas. The heart is already functioning, and continues to develop and change over this period of time. The respiratory system begins developing, as do blood vessels, blood cells, nervous and endocrine organs. Clearly, the most crucial organs of the human form are developing during organogenesis (Gajaan & Tossif, 2013).
  • 15. SBB 2114 14 3.0 FETAL DEVELOPMENT After the 8 week of embryonic development, the developing organism is called a fetus (fetal development. All major structures are already formed in the fetus, but they continue to grow and develop. Since the precursors of all the major organs are created by this time, the fetal period is described both by organ and by a list of changes by weeks of gestational age. This development divided into 2 main stages: second trimester (3 months) and third trimester (4 months). 3.1 Second Trimester: During the second trimester (the next three months of pregnancy) the bones actively enlarge and the brain develops a lot. During the second trimester until about 24 weeks, the fetus cannot live outside of the body because its lungs, heart and blood systems have not developed enough. The face looks more human, the baby has hair, the ears stand out, and the baby can hear the mother’s voice. Between 16 and 20 weeks, the baby’s movements may be felt. The baby begins to store some antibodies and this slowly increases until birth. Eyebrows and eyelashes appear. A fine downy hair (lanugo) appears all over the baby’s body (BC Ministry of Health [BCMOH], 2011). The baby’s skin is thin, shiny, and covered with a creamy protective coating called vernix. The baby’s legs lengthen, and move well. Teeth develop-enamel and dentine are being formed. By the end of the fifth month the baby is about half the length of a newborn. During the second trimester, meconium (the baby’s first stool) begins to appear in the intestines. The fetus has grown to about 175 millimeters in length and attained a weight of about 225 grams (Raven & Johnson, 2001). 3.2 Third Trimester: During the third trimester (the last 3 months of pregnancy is predominantly a period of growth rather than development. The weight of the fetus doubles several times, but this increase in bulk is not the only kind of growth that occurs. Most of the major nerve tracts in the brain, as well as many new neurons (nerve cells), are formed during this period. By week 28 the fetus can now store iron, calcium, and other nutrients and the fetus can hear and respond to sounds. After week 32 the male fetus’s testicles begin to drop into the scrotum and the pupils in the fetus’s eyes can react to light (BCMOH, 2011). Neurological growth is far from complete at the end of the third trimester, when birth takes place. The downy hair on the fetus’s body begins to disappear by week 36. The baby continues to increase the store of antibodies and is able to resist some diseases. The testicles of male fetus are now in the scrotum and the labia majora of female fetus are developed. The fetus is now full term at week 40. The lungs of fetus completly grown and the fetus starts to breath and try to come out from mother’s uterus (Meeks, 1982).
  • 16. SBB 2114 15 4.0 CONCLUSION From a single cell to a baby in 9 months; a developmental process that represents an amazing integration of increasingly complex phenomena. The study of these phenomena is called embryology, and the field includes investigations of the molecular, cellular, and structural factors contributing to the formation of an organism. These studies are important because they provide knowledge essential for creating health care strategies for better reproductive outcomes. Thus, our increasingly better understanding of embryology has resulted in new techniques for prenatal diagnoses and treatments, therapeutic procedures to circumvent problems with infertility, and mechanisms to prevent birth defects, the leading cause of infant mortality. These improvements in prenatal and reproductive health care are significant not only for their contributions to improved birth outcomes but also for their long- term effects postnatally. The development of human before birth divided into two: embryonic development which is from 1st week until 8th week (known as first trimester) and fetal development from 9th week until 37th week (known as second and third trimester). Embryonic period is also considered the organogenic period, when most organs within the embryo have begun to form. While fetal period is a time of extensive growth in size and mass as well as ongoing differentiation of organ systems established in the embryonic period. There are several stages in embryonic development which is germinal, gastrulation, neurulation and organogenesis stage. Germinal stage involves fertilization, cleavage and blastulation processes. While gastrulation stage involves formation of epiblast and hypoblast, movement and rearangement of blastomeres by changes of their position relative to one another and also extension of extraembryonic membrane by trophoblast, the cells of the embryo rearranged into three primary germ layers: ectoderm, mesoderm, and endoderm. After the gastrulation stage, neurulation stage occur, where the three primary cell layers undergoes transformation and differentiation to form the notochord and the hollow dorsal nerve cord. Lastly in embryonic development the organogenesis stage takes place, by which the ectoderm, endoderm, and mesoderm develop into the internal organs of the organism within week 3 to the end of week 8. After the 8 week of embryonic development, the fetal development will start. This development mainly for growing and development of organs. Fetus development divided into 2 main stages: second trimester (3 months) and third trimester (4 months). The critical stages of human development take place quite early, and the following six months are essentially a period of growth. The growth of the brain is not yet complete, however, by the end of the third trimester, and must be completed postnatally. (Total Words = 3500)
  • 17. SBB 2114 16 REFERENCES BC Ministry of Health, [BCMOH]. (2011). The best chance: Stages of pregnancy. Retrieved from: http://www.bestchance.gov.bc.ca/pregnancy/2nd-trimester/stages-of-pregnancy/3rd-trimester- baby.html. Betsy, T.L.H. (2009). Longman Essential Revision Guide for Exam Success Biology. Malaysia: Pearson Sdn. Bhd. Brevini, T.A.L., & Pennarossa, G. (2013). Gametogenesis, Early Embryo Development, and Stem Cell Derivation, SpringerBriefs in Stem Cells. DOI: 10.1007/978-1-4614-5532-5_2. Danton, H.(2010). Gastrulation: formation of the primary germ layers [PDF document]. Retrieved fromhttp://www.utm.utoronto.ca/~w3bio380/pdf/OLD-PDF/2010%20Summer/Gastrulation.pdf Embryogenesis. (n.d.). In Wikipedia. Retrieved May 20, 2016, from https://en.wikipedia.org/wiki/Embryogenesis Gajaan, S., & Tossif, G. (2013). Organogenesis Critical period of Organogenesis [PowerPoint slides]. Retrieved from www.slideshare.net/applevsamsung/organogenesis. Guus, V.D.B. (2011). Embryology: Early development from a phenomenological point of view. Netherlands: Bolk’s Companions. Retrieved from http://www.louisbolk.org/downloads/1281.pdf. Hill, M.A. (2015, November 16). Embryology Embryonic Development. UNSW Embryology [mediawiki]. Retrieved June 3, 2016, from https://embryology.med.unsw.edu.au/embryology/index.php/Embryonic_Development Louisiana State University Health Sciences Center New Orleans [LSUHSC]. (2012, November 30). The Stages of Human Embryonic Development. Virtual Human Embryo Project [www.ehd.org]. Retrieved from http://virtualhumanembryo.lsuhsc.edu/DREM/Contact_info_EHD.html. Marieb, E.N. (2006). Essential of Human Anatomy & Physiology. 8th ed. Addison Wesley Longman. Meeks, J. (1982). Family Living and Human Reproduction. Columbus, OH: Charles E. Merrill Pub. Co. Retrieved from http://www.edu.gov.mb.ca/k12/cur/physhlth/hs_k-8/blms/blm7-1-1.pdf. Pratheep, S. (2015). Chapter 4: General embryology- Animal [PowerPoint slides]. Lecture Notes. Raven, P.H., & Johnson, G.B. (2001). Biology: 6th edition. Retrieved from www.mhhe.com/biosci/genbio/raven6b/graphics/raven06b/other/raven06_60.pdf Sadler, T.W. (2012). Medical Embryology, 12th edition. Retrieved from http://medfile.ir/iran%20anatomy%20files/text/Langman's%20Medical%20Embryology%2012t h%20Edition%20(www.irananatomy.ir).pdf. Shamala, M.(2016). Developmental Biology: Chapter 1 [PowerPoint slides]. Lecture Notes. Taube, P.R.(n.d.). Ectoderm: Neurulation, Neural Tube, Neural Crest [PDF document]. Retrieved from http://www.columbia.edu/itc/hs/medical/humandev/2004/Chapt4-Ectoderm.pdf.