Germ cells are produced through meiosis which halves the number of chromosomes from 46 to 23. Fertilization restores the diploid number when a sperm and egg fuse. Mitosis duplicates DNA before cell division so each new cell has the full chromosome number. Meiosis involves two cell divisions without DNA replication between, resulting in four haploid gametes each with 23 chromosomes. Chromosomal abnormalities can arise from errors in meiosis or mitosis, causing conditions like Down syndrome, Turner syndrome, and others with characteristic physical and dental features.

1. GENERAL EMBRYOLOGY
Presented by
Dr. Sharmin Sultana
BDS, FCPS Part II Trainee
Dept of Orthodontics and Dentofacial
Orthopedics
Dhaka Dental College and Hospital

2. GENERAL EMBRYOLOGY
Germ Cell Formation and Fertilization
Humans have approxi- mately 23,000 genes on 46 chromosomes. In somatic
cells, chromosomes appear as 23 homologous pairs to form the diploid
number of 46 chromosome. There are 22 pairs of matching chromosomes, the
autosomes, and one pair of sex chromosomes. If the sex pair is XX, the
individual is genetically female; if the pair is XY, the individual is genetically
male. One chromosome of each pair is derived from the maternal gamete, the
oocyte, and one from the paternal gamete, the sperm. Thus, each gamete
contains a haploid number of 23 chromosomes, and the unión of the gametes
at fertilization restores the diploid number of 46. The process that produces
germ cells with half the number of chromosomes of the somatic cell is called
meiosis.

3. MITOSIS:
Before mitotic cell division
begins, DNA is first replicated
during the S (synthetic) phase
of the cell cycle so that the
amount of DNA is doubled to a
value known as tetraploid
(which is 4 times the amount
of DNA found in the germ cell).
During mitosis the
chromosomes containing this
tetraploid amount of DNA are
split and distributed equally
between the two resulting
cells; thus both cells have a
diploid DNA quantity and
chromosome number, which
duplicates the parent cell
exactly.

4. Meiosis: involve two sets of cell division.
DNA is replicated to the tetraploid value
Homologous chromosomes approach each other.
so that homologous chromosomes pair, and each
member of the pair consists of two chromatids.
Intimately paired homologous chromosomes
interchange chromatid fragments [crossover]. By
formation X like structure the chiasma.
Double-structured chromosomes pull apart.
Anaphase of the first meiotic división.
homologus pairs then separate into two daughter
cells. In the first division the number of
chromosomes is halved, and each daughter cell
contains a diploid amount of DNA quantity
chromosome number.
During the second meiotic división, the double-
structured chromosomes split at the centromere.
completion of división, each of the four daughter
cell, each gamet contain 23 single (haploid number)
chromosomes and haploid amount of DNA, each
cells are different from each other.

5. Birth defect : Chromosomal and Genetic Factors
Abnormalities in chromosome number may originate during meiotic or mitotic division.The process
occasionally malfunctions, producing zygotes with an abnormal number of chromosomes and
individuals with congenital defects that sometimes affect the mouth and teeth. For example, an
abnormal number of chromosomes can result from the failure of a homologous chromosome pair
to separate during meiosis,sometimes however separation does not occur (nondisjunction), and
both member of a pair move into one cell. so that the daughter cells contain 24 or 22
chromosomes. If, on fertilization, a gamete containing 24 chromosomes fuses with a normal
gamete (containing 23), the resulting zygote will possess 47 chromosomes; or 45 chromosome
one homologous pair has a third component. Thus the cells are trisomic for a given pair of
chromosomes. If one member of the homologous chromosome pair is missing, a rare condition
known as monosomy prevails.

6. The best known example of trisomy is Down syndrome, or trisomy 21.
 Among features of Down syndrome are growth retardation, mental retardation,
 craniofacial abnormalities like-facial clefts, a shortened palate, a protruding and
fissured tongue, and delayed eruption of teeth and hypodontia.
 Also have upward slantíng eyes, epícantlial folds (extra skin folds at the medial
corners of the eyes], fíat facies, and small ears; cardiac defects.
 These individuáis aiso have an increased chance of deveioping ieukemia, infections,
thyroid dysfunction, and premature aging. Furthermore, an increased frequency and
earlier onset of Aizheimer disease is observed among persons with Down syndrome.
Trisomy 13
The main abnormalities of trisomy 13 are intellectual
dísability, holoprosencephaly, congenital heart defects,
deafness, cleft lip and palate, and eye defects, such as
microphthal- mia. anophthalmia, and coloboma.The
incidente of this abnormality is approximately 1 in 20,000
live births, and more than 90% of the infants die in the
first month after birth. Approximately 5% live beyond 1
year.

7. TURNER Syndrome
 Turner syndrome, with a 45, X karyotype, Is the oniy monosomy compatible with life.
 Even then, 98% of all fetuses with the syndrome are spontaneously aborted. The few
that survive are unmistakably female in appearance and are characterized by the
absence of ovaries (gonadal dysgenesis) and short stature.
 Other common associated abnormalities are webbed neck, lymphedema of the
extremities, skeletal deformities, and a broad chest with widely spaced nipples.
Approximately 10% of all human malformations are caused by an alteration in a single
gene. Such alterations are transmitted in several ways, of which two are of special
importance. First, if the malformation results from autosomal dominant inheritance, the
affected gene generally is inherited from only one parent. The trait usually appears in
every generation and can be transmitted by the affected parent to statistically half of the
children.

8.  Examples of autosomal dominant conditions include- achondroplasia, cleidocranial dysostosis,
Cherubism, osteogenesis imperfecta, dentinogenesis imperfect and some forms of
amelogenesis imperfecta; the latter two conditions result in abnormal formation of the dental
hard tissues.
 Second, when the malformation is due to autosomal recessive inheritance, the abnormal gene
can express itself only when it is received from both parents. Examples include
chondroectodermal dysplasia, some cases of microcephaly, and cystic fibrosis.
ACHONDROPLASIA
 A common type of genetic dwarfism
 Failure of proliferation of cartilage in epiphyses and base of skull
 Short limbs but normal sized skull
 Middle third of face retrusive due to deficient growth of skull base, profile to be concave.
 The mandible often protrusive
 Usually severe malocclusion

9. Cleidocranial Dysostosis
 Rare genetic disorder causing defective
formation of clavicles
 Delayed closure of fontanelles and
other defects
 Many permanent teeth typically remain
embedded in the jaw
 Many additional unerupted teeth also present
 Sometimes many dentigerous cysts

10. Cherubism
 Inherited as autosomal dominant
trait
 Jaw swellings appear in infancy
 Angle regions of mandible affected
symmetrically giving chubby face
 Symmetrical involvement of maxilla
also in more severe cases
 Teeth are frequently displaced and
maybe loosened
 Radiographically, lesions appear as
multilocular cyst like areas

11. Amelogenesis imperfecta
 Inheritance can be autosomal dominant, recessive or x- linked. However, the most
common types have an autosomal inheritance and are thought to be caused by
mutations in the AMEL-X gene, which codes for ameloblastin (C4), enamelin (C4) or
tuftelin (C1). In the case of autosomal dominant type of amelogenesis imperfect, the
locus of the defective gene is on chromosome 4q 21 to which enamelin maps.
1. Hypoplastic amelogenesis imperfecta
 Enamel is randomly pitted, grooved, or very thin
 Enamel is hard and translucent
 Stained
 Teeth are not especially susceptible to caries
2. Hypomaturation amelogenesis imperfecta
 The enamel is normal in form
 Opaque, white to brownish-yellow
 Mottled fluoride effects
 Soft and vulnerable to attrition

12. 3. Hypocalcified amelogenesis imperfect
 Enamel form in normal quantity but poorly
calcified
 Normal in thickness, but weak and opaque
or chalky appearance
 Teeth tend to stain
 Relatively rapid worn away
 Incisors may acquire a shouldered form
Dentinogenesis Imperfecta
 Dentine is soft
 Tooth discoloration and attrition is less severe
in permanent teeth
 Class III malocclusion is associated in over 70%
 Dental development delayed in 20%

13. Osteogenesis imperfect ( brittle bone syndrome)
 The fragile bones due to inadequate type I collagen foemation
 Multiple fractures typically lead to gross deformities
 Variable degrees of dentinogenesis imperfecta associated type III and Iv
FORMATION OF THE THREE-LAYERED EMBRYO
 After fertilization, mammalian development involves a phase of rapid proliferation and
migration of cells,
 little or no differentiation.
 This proliferative phase lasts until three germ layers have formed.
 In summary, the fertilized egg initially undergoes a series of rapid divisions that lead
to the formation of a ball of cells called the MORULA.

14. Formation of the three-layered embryo cont…..
Morula Fluid seeps into the morula cells realign themselves to form a fluid-filled
hollow ball, called blastocyst Two cell populations now can be distinguished within
the blastocyst: those lining the cavity (the primary yolk sac), called trophooblast cells
and a small cluster within the cavity, called the inner cell mass or embryoblast .
The embryoblast cells form the embryo proper, whereas the trophoblast cells are
associated with implantation of the embryo and formation of the placenta;

15. Formation of the three-layered embryo
cont…..
 At about day 8 of gestation, the cells of
the embryoblast differentiate into a
two-layered disk, called the bilaminar
germ disk.
 The cells situated dorsally, or
ectodermal layer, are columnar and
reorganize to form the amniotic cavity.
 Those on the ventral aspect, the
endodermallayer, are cuboidal and
form the roof of a second cavity (the
secondary yolk sac), which develops
from the migration of peripheral cells of
the extra embryonic endodermal layer.
 This configuration is completed after 2
weeks of development. During that
time the axis of the embryo is
established and is represented by a
slight enlargement of the ectodermal
and endodermal cells at the head (or
rostral) end of the embryo in a region
known as the prochordal plate.

16. Formation of the three-layered embryo
cont…..
 During the third week of development
the bilaminar embryonic disk is
converted to a trilaminar disk. the floor
of the amniotic cavity is formed by
ectoderm, and within it a structure called
the primitive streak develops along the
midline.

17.  This structure is a narrow groove with
slightly bulging areas on each side.
The rostral end of the streak finishes
in a small depression called the
primitive node, or pit. Cells of the
ectodermal layer divide at the node
and migrate between the ectoderm
and endoderm to form a solid column
that pushes forward in the midline as
far as the prochordal plate. Through
canalization of this cord of cells, the
notochord is formed to support the
primitive embryo.

18.  Elsewhere alongside the primitive streak,
cells of the ectodermal layer divide and
migrate toward the streak, where they
invaginate and spread laterally between
the ectoderm and endoderm. These cells,
sometimes called the mesoblast, infiltrate
and push away the extraembryonic
endodermal cells of the hypoblast, except
for the prochordal plate, to form the true
embryonic endoderm.
 They also pack the space between the
newly formed embryonic endoderm and
the ectoderm to form a third layer of cells,
the mesoderm . In addition to spreading
laterally, cells spread progressively
forward, passing on each side of the
notochord and prochordal plate. The cells
that accumulate anterior to the prochordal
plate as a result of this migration give rise
to the cardiac plate, the structure in which
the heart forms. As a result of these cell
migrations, the notochord and mesoderm
now completely separate the ectoderm
from the endoderm , except in the region
of the prochordal plate and in a similar
area of fusion at the tail (caudal) end of the
embryo, the cloacal plate.

19. Derivatives of the germ
layers and neural crest.

20. Neural Crest Derivatives
1. Cranial nerve ganglia.
2. Spinal [dorsal root] ganglia
3. Sympathetic chain and preaortic ganglia
4. Parasympathetic ganglia of the gastrointestinal tract
5. Meninges [forebrain], arachnoid meter and pia meter, duremetter, leptomeninges.
6. Schwann cells
7. Glial cells
8. Connective tissue and bones of the face and skull
9. Dermis in face and neck
10. Melanocytes
11. Smooth muscle cells to blood vessels of the face and forebrain
12. Odontobiasts (dentin), cement, pulp, alveolar bone, and periodontal ligament.
13. C cells of the thyroid gland
14. Conotruncal septum in the heart
15. Adrenal medulla

21. Neural Crest Cell Problems
 As the neural tube forms, a group of cells separate from the neuroectoderm.
 These cells have the capacity to migrate and differentiate extensively within the
developing embryo, and they are the basis for structures such as the spinal sensory
ganglia, sympathetic neurons, Schwann cells, pigment cells, and meninges. In the
avian embryo these cells can be distinguished differentiating and separating at the
crest of the neural folds, hence the name neural crest cells.
 Neural crest cells in the head region have an important role. In addition to assisting in
the formation of the cranial sensory ganglia, they also differentiate to form most of the
connective tissue of the head.
 Embryonic connective tissue elsewhere is derived from mesoderm and is known as
mesenchyme, whereas in the head it is known as ectomesenchyme, reflecting its
origin from neuroectoderm.
 In a dental context the proper migration of neural crest cells is essential for the
development of the face and the teeth. All the tissues of the tooth(except enamel and
perhaps some cementum) and its supporting apparatus are derived directly from
neural crest cells, and their depletion prevents proper dental development.

22. Neural Crest Cell Problems cont…..
 At the completion of the miqration of the neural crest cells in the fourth week of human
embryonic life, they form practically all of the loose mesenchymal tissue in the facial region that
lies between the surface ectoderm and the underlying forebrain and eye and most of the
mesenchyme in the mandibular arch. Most of the neural crest cells in the facial area later
differentiate into skeletal and connective tissues, including the bones of the jaw and the teeth.
 The importance of neural crest migration and the possibility of drug-induced impairment has
been demonstrated clearly by unfortunate experience.In the 1960s and 70s, exposure to
thalidomide caused major congenital defects including facial anomalies in thousands of children.
In the 1980s, severe facial malformations related to the anti-acne drug isotretinoin (Accutane)
were reported. The similarities in the defects make it likely that both these drugs affect the
formation and/or migration of neural crest cells.

23. Mandibulofacial dysostosis (Treacher Collins syndrome)
 Altered neural crest development also has been implicated in mandibulofacial dysostosis
(Treacher Collins syndrome) .
 In Treacher Collins syndrome, both the maxilla and mandible are underdeveloped as a result
of a generalized lack of mesenchymal tissue.
 Enlarged tongue, possible cleft palate.
 Lack of middle ear development which results in loss of hearing.
 The best evidence suggests that the problem arises because of excessive cell death (cause
unknown) in the trigeminal ganglion, which secondarily affects neural crest-derived cells.

24. Pierre Robin syndrome
 extremely small mandible at birth.
 usually accompanied by a cleft palate because the
restriction on displacement of the mandible forces
the tongue upward and prevents normal closure of
the palatal shelves.
 The reduced volume of the oral cavity can lead to
respiratory difficulty at birth, and it may be
necessary to perform a tracheostomy so the infant
can breathe.
 Early mandibular advancement via distraction
osteogenesis has been used recently in these
severely affected infants to provide more space for
an airway so that the tracheostomy can be closed.
 It has been estimated that about one-third of the
Pierre Robin patients have a defect in cartilage
formation and can be said to have Stickler
syndrome. Not surprisingly, this group have limited
growth potential. Catch-up growth is most likely
when the original problem was mechanical growth
restriction that no longer existed after birth.

25. Neural Crest Cell Problems cont…..
Hemifacial microsomia
 Hemifacial microsomia, as the name suggests,
is primarily a unilateral and always an
asymmetrical problem.
 It is characterized by a lack of tissue on the
affected side of the face.
 Typically, the external ear is deformed and both
the ramus of the mandible and associated soft
tissues (muscle, fascia) are deficient or missing.
 An early explanation of the condition was that it
was due to hemorrhage from the stapedial artery
at the time, about 6 weeks after conception,
when the ma-xillary artery takes over the blood
supply to the affected area.
 More recent work suggests that, although
hemorrhage at the critical time may be involved,
hemifacial microsomia arises primarily from early
loss of neural crest cell.

26. To be continued………..