The document summarizes key stages in the development of the neural tube and brain during embryogenesis. It discusses how the neural tube forms from the ectoderm and closes, forming the brain vesicles and flexures that give rise to the distinct brain regions. It describes the migration and differentiation of cells from the alar and basal plates that develop into various neuronal populations and structures of the brainstem and spinal cord. The formation and differentiation of the cerebellum, pons, midbrain, hindbrain, diencephalon and telencephalon are also covered. Critical signaling molecules that pattern the early neural tube are also mentioned.
4 th ventricle- Anatomical and surgical perspectivesuresh Bishokarma
4th ventricle connects the entire ventricular system of brain. Its connection with cisterns magna and cerebella pontine cistern via foramen of magenta and Luschka. CSF absorbs into the arachnoid granulation.
4 th ventricle- Anatomical and surgical perspectivesuresh Bishokarma
4th ventricle connects the entire ventricular system of brain. Its connection with cisterns magna and cerebella pontine cistern via foramen of magenta and Luschka. CSF absorbs into the arachnoid granulation.
USMLE neuroanatomy neuroanatomy 019 CNS development .pdfAHMED ASHOUR
The development of the CNS is a fascinating process that occurs during embryonic development and continues into early childhood.
Disruptions or abnormalities during this process can lead to a wide range of neurological disorders and developmental disabilities.
Understanding the mechanisms underlying CNS development is critical for advancing our knowledge of brain development and for developing new therapies for neurological disorders.
Richard's aventures in two entangled wonderlandsRichard Gill
Since the loophole-free Bell experiments of 2020 and the Nobel prizes in physics of 2022, critics of Bell's work have retreated to the fortress of super-determinism. Now, super-determinism is a derogatory word - it just means "determinism". Palmer, Hance and Hossenfelder argue that quantum mechanics and determinism are not incompatible, using a sophisticated mathematical construction based on a subtle thinning of allowed states and measurements in quantum mechanics, such that what is left appears to make Bell's argument fail, without altering the empirical predictions of quantum mechanics. I think however that it is a smoke screen, and the slogan "lost in math" comes to my mind. I will discuss some other recent disproofs of Bell's theorem using the language of causality based on causal graphs. Causal thinking is also central to law and justice. I will mention surprising connections to my work on serial killer nurse cases, in particular the Dutch case of Lucia de Berk and the current UK case of Lucy Letby.
Slide 1: Title Slide
Extrachromosomal Inheritance
Slide 2: Introduction to Extrachromosomal Inheritance
Definition: Extrachromosomal inheritance refers to the transmission of genetic material that is not found within the nucleus.
Key Components: Involves genes located in mitochondria, chloroplasts, and plasmids.
Slide 3: Mitochondrial Inheritance
Mitochondria: Organelles responsible for energy production.
Mitochondrial DNA (mtDNA): Circular DNA molecule found in mitochondria.
Inheritance Pattern: Maternally inherited, meaning it is passed from mothers to all their offspring.
Diseases: Examples include Leber’s hereditary optic neuropathy (LHON) and mitochondrial myopathy.
Slide 4: Chloroplast Inheritance
Chloroplasts: Organelles responsible for photosynthesis in plants.
Chloroplast DNA (cpDNA): Circular DNA molecule found in chloroplasts.
Inheritance Pattern: Often maternally inherited in most plants, but can vary in some species.
Examples: Variegation in plants, where leaf color patterns are determined by chloroplast DNA.
Slide 5: Plasmid Inheritance
Plasmids: Small, circular DNA molecules found in bacteria and some eukaryotes.
Features: Can carry antibiotic resistance genes and can be transferred between cells through processes like conjugation.
Significance: Important in biotechnology for gene cloning and genetic engineering.
Slide 6: Mechanisms of Extrachromosomal Inheritance
Non-Mendelian Patterns: Do not follow Mendel’s laws of inheritance.
Cytoplasmic Segregation: During cell division, organelles like mitochondria and chloroplasts are randomly distributed to daughter cells.
Heteroplasmy: Presence of more than one type of organellar genome within a cell, leading to variation in expression.
Slide 7: Examples of Extrachromosomal Inheritance
Four O’clock Plant (Mirabilis jalapa): Shows variegated leaves due to different cpDNA in leaf cells.
Petite Mutants in Yeast: Result from mutations in mitochondrial DNA affecting respiration.
Slide 8: Importance of Extrachromosomal Inheritance
Evolution: Provides insight into the evolution of eukaryotic cells.
Medicine: Understanding mitochondrial inheritance helps in diagnosing and treating mitochondrial diseases.
Agriculture: Chloroplast inheritance can be used in plant breeding and genetic modification.
Slide 9: Recent Research and Advances
Gene Editing: Techniques like CRISPR-Cas9 are being used to edit mitochondrial and chloroplast DNA.
Therapies: Development of mitochondrial replacement therapy (MRT) for preventing mitochondrial diseases.
Slide 10: Conclusion
Summary: Extrachromosomal inheritance involves the transmission of genetic material outside the nucleus and plays a crucial role in genetics, medicine, and biotechnology.
Future Directions: Continued research and technological advancements hold promise for new treatments and applications.
Slide 11: Questions and Discussion
Invite Audience: Open the floor for any questions or further discussion on the topic.
A brief information about the SCOP protein database used in bioinformatics.
The Structural Classification of Proteins (SCOP) database is a comprehensive and authoritative resource for the structural and evolutionary relationships of proteins. It provides a detailed and curated classification of protein structures, grouping them into families, superfamilies, and folds based on their structural and sequence similarities.
Professional air quality monitoring systems provide immediate, on-site data for analysis, compliance, and decision-making.
Monitor common gases, weather parameters, particulates.
This pdf is about the Schizophrenia.
For more details visit on YouTube; @SELF-EXPLANATORY;
https://www.youtube.com/channel/UCAiarMZDNhe1A3Rnpr_WkzA/videos
Thanks...!
Richard's entangled aventures in wonderlandRichard Gill
Since the loophole-free Bell experiments of 2020 and the Nobel prizes in physics of 2022, critics of Bell's work have retreated to the fortress of super-determinism. Now, super-determinism is a derogatory word - it just means "determinism". Palmer, Hance and Hossenfelder argue that quantum mechanics and determinism are not incompatible, using a sophisticated mathematical construction based on a subtle thinning of allowed states and measurements in quantum mechanics, such that what is left appears to make Bell's argument fail, without altering the empirical predictions of quantum mechanics. I think however that it is a smoke screen, and the slogan "lost in math" comes to my mind. I will discuss some other recent disproofs of Bell's theorem using the language of causality based on causal graphs. Causal thinking is also central to law and justice. I will mention surprising connections to my work on serial killer nurse cases, in particular the Dutch case of Lucia de Berk and the current UK case of Lucy Letby.
Cancer cell metabolism: special Reference to Lactate PathwayAADYARAJPANDEY1
Normal Cell Metabolism:
Cellular respiration describes the series of steps that cells use to break down sugar and other chemicals to get the energy we need to function.
Energy is stored in the bonds of glucose and when glucose is broken down, much of that energy is released.
Cell utilize energy in the form of ATP.
The first step of respiration is called glycolysis. In a series of steps, glycolysis breaks glucose into two smaller molecules - a chemical called pyruvate. A small amount of ATP is formed during this process.
Most healthy cells continue the breakdown in a second process, called the Kreb's cycle. The Kreb's cycle allows cells to “burn” the pyruvates made in glycolysis to get more ATP.
The last step in the breakdown of glucose is called oxidative phosphorylation (Ox-Phos).
It takes place in specialized cell structures called mitochondria. This process produces a large amount of ATP. Importantly, cells need oxygen to complete oxidative phosphorylation.
If a cell completes only glycolysis, only 2 molecules of ATP are made per glucose. However, if the cell completes the entire respiration process (glycolysis - Kreb's - oxidative phosphorylation), about 36 molecules of ATP are created, giving it much more energy to use.
IN CANCER CELL:
Unlike healthy cells that "burn" the entire molecule of sugar to capture a large amount of energy as ATP, cancer cells are wasteful.
Cancer cells only partially break down sugar molecules. They overuse the first step of respiration, glycolysis. They frequently do not complete the second step, oxidative phosphorylation.
This results in only 2 molecules of ATP per each glucose molecule instead of the 36 or so ATPs healthy cells gain. As a result, cancer cells need to use a lot more sugar molecules to get enough energy to survive.
Unlike healthy cells that "burn" the entire molecule of sugar to capture a large amount of energy as ATP, cancer cells are wasteful.
Cancer cells only partially break down sugar molecules. They overuse the first step of respiration, glycolysis. They frequently do not complete the second step, oxidative phosphorylation.
This results in only 2 molecules of ATP per each glucose molecule instead of the 36 or so ATPs healthy cells gain. As a result, cancer cells need to use a lot more sugar molecules to get enough energy to survive.
introduction to WARBERG PHENOMENA:
WARBURG EFFECT Usually, cancer cells are highly glycolytic (glucose addiction) and take up more glucose than do normal cells from outside.
Otto Heinrich Warburg (; 8 October 1883 – 1 August 1970) In 1931 was awarded the Nobel Prize in Physiology for his "discovery of the nature and mode of action of the respiratory enzyme.
WARNBURG EFFECT : cancer cells under aerobic (well-oxygenated) conditions to metabolize glucose to lactate (aerobic glycolysis) is known as the Warburg effect. Warburg made the observation that tumor slices consume glucose and secrete lactate at a higher rate than normal tissues.
1. Submitted To: Dr. Vasudha
By: Komalpreet Kaur
Roll no: 27231979013
MSc. 3rd Semester
Department : Human Genetics
2. a. The onset of gastrulation is marked by the formation of the primitive streak and the primitive node. The
primitive streak provides an opening to deeper embryonic layers.
b. The migrating cells first move to the primitive streak and then change direction and move down and under
the upper layer
c. Once under the upper layer, the cells change direction and begin migrating rostrally under the upper layer
(blue arrows).
d. Cells that migrate along the axial midline send molecular signals that induce cells in the overlying epiblast
layer to differentiate into neuroectodermal cells (red band) which are the neural progenitor cells.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2989000/
E- cadherin
FGF8
3. • At the beginning of the third week
CNS appears from thickened
ectoderm with the neural plate in the
mid-dorsal region in front of the
primitive node.
• Its lateral edges elevate to form the
neural folds.
• With further development, the neural
folds continue to elevate, approach
each other in the midline, and finally
fuse, forming the neural tube
Developmental Biology. 6th edition.
Gilbert SF.
Fig: Primary neurulation:
neural tube formation in the
chick embryo
4. • Secondary neurulation :Fusion begins in
the cervical region and proceeds in
cephalic and caudal directions .
• Closure of the cranial neuropore -18 to 20-
somite stage (25thday);
• caudal neuropore -approximately 3 days
later.
• Human neural tube closure requires a
complex interplay between genetic and
environmental factors. Certain genes, such
as Pax3, sonic hedgehog, and openbrain,
are essential for the formation of the
mammalian neural tube, but dietary
factors, such as cholesterol and folic acid,
also appear to be critical.
Fig :Dorsal views of neurulating embryos at
different stages of neural tube closure
Embryology of neural tube development
T.W. Sadler
https://doi.org/10.1002/ajmg.c.30049
5. • Failure to close the human posterior neural
tube regions at day 27 (or the subsequent
rupture of the posterior neuropore shortly
thereafter) results in a condition called spina
bifida
• Failure to close the anterior neural tube
regions results in a lethal condition,
anencephaly. Here, the forebrain remains in
contact with the amniotic fluid and
subsequently degenerates.
• The failure of the entire neural tube to close
over the entire body axis is called
craniorachischisis.
• Encephalocele is a sac-like protrusion of the
brain and brain membranes (tissue that
covers and protect the brain) through an
opening in the skull.
It has been estimated that 50% of human neural
tube defects could be prevented by a pregnant
woman's taking supplemental folic acid (vitamin
B12), and the U.S. Public Health Service
recommends that all women of childbearing age
take 0.4 mg of folate daily to reduce the risk of
neural tube defects during pregnancy.
(Multivitamin/folic acid supplementation in early
pregnancy reduces the prevalence of neural tube
defects) PMID: 2478730 DOI:
10.1001/jama.262.20.2847
7. Fig :Changes in the morphology of
the embryo in the embryonic
period. The formation of the neural
tube occurs between E19 and E29.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2
989000/
8.
9. Rapid growth folds the neural tube forming 3 brain flexures
cephalic flexure - in the midbrain region
cervical flexure - between hindbrain and spinal cord
pontine flexure - between metencephalon and
myelencephalon
The lumen of the spinal cord, the central canal is continuous with that of the brain
vesicles. The cavity of the rhombencephalon is the fourth ventricle, that of the
diencephalon is the third ventricle, and those of the cerebral hemispheres are the
lateral ventricles
The lumen of the mesencephalon connects the third and fourth ventricles and is very
narrow and is then known as the aqueduct of Sylvius.
Each lateral ventricle communicates with the third ventricle through the
interventricular foramina of Monro
11. • roof plate - dorsal region
• alar plate - dorsal lateral region (sensory input fine
touch, proprioception, and vibration)
• basal plate - ventral lateral region (motor output to
skeletal muscle)
• floor plate - ventral region
• sulcus limitans : longitudinal groove which marks the
boundaries between two.
• roof plate region - signals from surface ectoderm
• alar plate region - signals from surface ectoderm
• basal plate region - signals from the notochord and
floor plate
• floor plate region - signals from the notochord
Scanning electron micrographs of the Carnegie stages of
the early human embryos are reproduced with the
permission of Prof Kathy Sulik, from embryos collected
by Dr. Vekemans and Tania Attié-Bitach
12. The rhombencephalon consists of the
myelencephalon, the most caudal of the
brain vesicles, and the metencephalon,
which extends from the pontine flexure to
the rhombencephalic isthmus.
• The myelencephalon is a brain vesicle
that gives rise to the medulla oblongata.
• The ventral area of the medulla contains
a pair of fiber bundles (pyramids) that
consist of corticospinal fibers descending
from the developing cerebral cortex.
MYELENCEPHALON
METENCEPHALON
Fig : Lateral view of the brain vesicles in an 8-week embryo
(crown-rump length ~27 mm).
Langman's Medical Embryology
Author(s): T.W. Sadler
13. Fig :A, Sketch of the developing brain at the end of the fifth week of gestation shows the three primary divisions
of the brain and brain flexures. B, Transverse section of the caudal part of the myelencephalon (developing closed part
of medulla).C and D, Similar sections of the rostral part of the myelencephalon (developing open part of medulla) show
the position and successive stages of differentiation of the alar and basal plates.
THE DEVELOPING HUMAN CLINICALLY ORIENTED EMBRYOLOGY
Mark G. Torchia, T.V.N. (Vid) Persaud ,Keith L. Moore,
14. somatic efferent
group
• In the myelencephalon, it includes neurons of the hypoglossal (XII) nerve that supply the
tongue musculature. In the metencephalon and the mesencephalon, the column contains
neurons of the abducens (VI) trochlear (IV), and oculomotor(III) nerves respectively. These
nerves supply the eye musculature.
special visceral
efferent group
• Its motor neurons supply striated muscles of the pharyngeal arches. In the myelencephalon,
the column is represented by neurons of the accessory (XI), vagus (X), and
glossopharyngeal (IX) nerves.
general visceral
efferent
• The general visceral efferent group contains motor neurons that supply involuntary
musculature of the respiratory tract, intestinal tract, and heart
BASAL PLATE ( motor neurons)
15. somatic
afferent
(general
sensory)
group
• receives sensations of pain, temperature, and touch from the
pharynx by way of the glossopharyngeal nerve (IX).
Special
afferent
group
• receives impulses from taste buds of the tongue, palate,
oropharynx, and epiglottis and from the vestibulocochlear nerve
(VIII) for hearing and balance.
visceral
afferent,
group
• receives interoceptive information from the gastrointestinal tract
and heart.
ALAR PLATE ( sensory neurons)
16. The roof plate of the myelencephalon consists of a single layer of ependymal
cells covered by vascular mesenchyme, the pia mater.
tela choroidea.
choroid plexus which produces cerebrospinal
fluid. fluid
17. Fig :Photomicrograph of a transverse section through the diencephalon and
cerebral vesicles of a human embryo(approximately 50 days) at the level of the
interventricular foramina
THE DEVELOPING HUMAN
CLINICALLY ORIENTED
EMBRYOLOGY
Mark G. Torchia, T.V.N. (Vid)
Persaud ,Keith L. Moore,
18. • Two components form
• (1) the cerebellum, a coordination
center for posture and movement ,
and
• (2) the pons, the pathway for
nervefibers between the spinal cord
and the cerebral and cerebellar
cortices.
• The marginal layer of the basal plates
of the metencephalon expands as it
makes a bridge for nerve fibers
connecting the cerebral cortex and
cerebellar cortex with the spinal cord.
19. (1) the medial somatic
efferent group, which gives
rise to the nucleus of the
abducens nerve;
(2) the special visceral
efferent group, containing
nuclei of the trigeminal
and facial nerves, which
innervate the musculature of
the first and second
pharyngeal arches;
(3) the general visceral
efferent group,
with axons that supply the
submandibular and
sublingual glands.
(1) a lateral
somatic afferent
group, which
contains neurons of
the trigeminal nerve
2) the special
afferent group
3)the general
visceral
afferent group
ALAR PLATE
BASAL PLATE
20. •The dorsolateral parts of the alar plates
bend medially and form the rhombic
lips .
• As a result of a further deepening of
the pontine flexure, the rhombic lips
compress cephalocaudally and form the
cerebellar plate .
• In a 12-week embryo, this plate shows
a small midline portion, the vermis,
and two lateral portions, the
hemispheres.
•A transverse fissure soon separates the
nodule from the vermis and the lateral
flocculus from the hemispheres.
21. Fig: A, Sketch of the developing brain at the end of the fifth week. B, Transverse section of the metencephalon
(developing pons and cerebellum) shows the derivatives of the alar and basal plates. C and D, Sagittal sections of the hindbrain at 6 and 17 weeks,
respectively, show successive stages in the development of the pons and cerebellum.
THE DEVELOPING HUMAN CLINICALLY ORIENTED EMBRYOLOGY
Mark G. Torchia, T.V.N. (Vid) Persaud ,Keith L. Moore,
22. The structure of the cerebellum reflects its phylogenetic
(evolutionary) development
The archicerebellum (flocculonodular lobe), the oldestpart
phylogenetically, has connections with the vestibular apparatus, especially
the vestibule of the ear.
The paleocerebellum (vermis and anterior lobe), of more recent
development, is associated with sensory data from the limbs.
The neocerebellum (posterior lobe), the newest partphylogenetically, is
concerned with selective control of limb movements.
23. Fig: Sagittal sections through the roof of the
metencephalon showing development of the
cerebellum
Langman's Medical Embryology
Author(s): T.W. Sadler
24. • The marginal layer of each basal plate enlarges and forms the crus cerebri. These
crura serve as pathways for nerve fibers descending from the cerebral cortex to lower
centers in the pons and spinal cord.
• Initially, the alar plates of the mesencephalon appear as two longitudinal elevations
separated by a shallow midline depression . With further development, a transverse
groove divides each elevation into an anterior (superior) and a posterior(inferior)
colliculus .
• The posterior colliculi serve as synaptic relay stations for auditory reflexes; the
anterior colliculi function as correlation and reflex centers for visual impulses.
Fig: 3 A,B. Position and
differentiation of the
basal and alar plates in
the mesencephalon at
various stages of
development
Langman's Medical Embryology
Author(s): T.W. Sadler
25. • The prosencephalon consists of
the
• telencephalon, which forms the
cerebral hemispheres and
• diencephalon, which forms the
optic cup and stalk, pituitary,
thalamus, hypothalamus, and
epiphysis.
26. Fig: A. Medial surface of the right half of the prosencephalon in a 7-week embryo. B.
Transverse section through the prosencephalon
Langman's Medical Embryology
Author(s): T.W. Sadler
27. • The alar plates form the lateral walls of the diencephalon. A groove, the
hypothalamic sulcus,divides the plate into a dorsal and a ventral region, the
thalamus and hypothalamus, respectively.
• As a result of proliferative activity, the thalamus gradually projects into the lumen of
the diencephalon. Frequently, this expansion is so great that thalamic regions from
the right and left sides fuse in the midline, forming the massaintermedia, or
interthalamic connexus.
• The hypothalamus, forming the lower portion of the alar plate, differentiates into a
number of nuclear areas that regulate the visceral functions, including sleep,
digestion, body temperature, and emotional behavior. One of these groups, the
mamillary body, forms a distinct protuberance on the ventral surface of the
hypothalamus on each side of the midline.
28. • The diencephalon, develops from median portion of the prosencephalon
is thought to consist of a roof plate and two alar plates but to lack floor
and basal plates.
-The most caudal part of the roof plate which is
initially appears as an epithelial thickening in the midline, but by the
seventh week, it begins to evaginate .
• Serves as a channel through which light and darkness affect endocrine and
behavioral rhythms. In the adult, calcium is frequently deposited in the
epiphysis (landmark on radiographs of the skull.)
29. • The hypophysis, or pituitary gland, develops from two completely different parts:
An upgrowth from the ectodermal roof of the stomodeum, the hypophyseal diverticulum
(Rathke pouch)
A downgrowth from the neuroectoderm of the diencephalon, the neurohypophyseal
diverticulum
• Cells increase in number form anterior lobe of hypopysis-adenohypophysis
• small extension of this lobe forms pars tuberalis
• posterior wall of Rathke's pouch forms pars intermedia
• Infundibulum gives rise to stalk and pars nervosa, or posterior lobe of hypophysis.
30. Fig : Diagrammatic sketches illustrate development of
the pituitary gland. A, Sagittal section of the cranial end
of an embryo at approximately 36 days shows the
hypophyseal diverticulum, an upgrowth from the
stomodeum, and the neurohypophyseal diverticulum, a
downgrowth from the forebrain.
B to D, Successive stages of the developing pituitary
gland. By 8 weeks, th diverticulum loses its connection
with the oral cavity and is in close contact with the
infundibulum and posterior lobe (neurohypophysis)
of the pituitary gland.
E and F, Sketches of later stages show proliferation of
the anterior wall of the hypophyseal diverticulum to
form anterior lobe (adenohypophysis) of the pituitary
gland
THE DEVELOPING HUMAN CLINICALLY
ORIENTED EMBRYOLOGY
Mark G. Torchia, T.V.N. (Vid) Persaud ,Keith L.
Moore,
31. • FGF8, BMP4, and WNT5A from the diencephalon are
involved in the formation of the anterior and intermediate
lobes of the pituitary gland.
• The LIM homeobox gene LHX2 appears to control
development of the posterior lobe.
THE DEVELOPING HUMAN CLINICALLY
ORIENTED EMBRYOLOGY
Mark G. Torchia, T.V.N. (Vid) Persaud ,Keith L.
Moore,
32. Consist of two lateral outpocketings
- cerebral hemisphere
Median portion -lamina terminales.
• Cerebral hemispheres:
• begin as a bilateral evagintions of lateral walls of prosencephalon
• basal part begins to grow and bulges into lumen of lateral ventricle and into the
floor of foramen of monro.
• rapid growing region has a straited apperance , known as corpus straitum.
• The choroid plexus form the roof of diencephalon , but due to disapropriate
growth it protudes into lateral ventricle along choroidal fissure.
• The wall of hemisphere thickens above the fissure to form hippocampus (
olfaction)
33. Fig:Medial surface of the right half of the telencephalon and diencephalon in a 8 week and 10-week embryo
The corpus striatum expands
posteriorly and is divided into two parts: (1) a dorsomedial portion, the caudate
nucleus and (2) a ventrolateral portion, the lentiform nucleus . The
fiber bundle thus formed is known as the internal capsule
Langman's Medical Embryology
Author(s): T.W. Sadler
34. Fig:Development of gyri and sulci on the lateral surface of the cerebral
hemisphere. A. 7 months. B. 9 months.
• Continuous growth of the cerebral
hemispheres in anterior, dorsal,
and inferior directions results in
the formation of frontal, temporal,
and occipital lobes, respectively.
• As growth in the region overlying
the corpus striatum slows,
however, the area between the
frontal and temporal lobes
becomes depressed and is known
as the insula .
• During the final part of fetal life,
the surface of the cerebral
hemispheres grows so rapidly that
a great many convolutions
(gyri)separated by fissures and
sulci appear on its surface
Langman's Medical Embryology
Author(s): T.W. Sadler
35. • The cerebral cortex develops from the pallium
which has two regions:
(1) the paleopallium, or archipallium, immediately
lateral to the corpus striatum , and
(2) the neopallium, between the hippocampus and the
paleopallium
• In the neopallium, waves of neuroblasts migrate to
a subpial position and then differentiate into fully
mature neurons.
• When the next wave of neuroblasts arrives, they
migrate through the earlier-formed layers of cells
until they reach the subpial position. Hence, the
early-formed neuroblasts obtain a deep position in
the cortex, while those formed later obtain a more
superficial position.
Fig: Transverse section through the hemisphere and
diencephalon
Langman's Medical Embryology
Author(s): T.W. Sadler
36. • The walls of the developing cerebral
hemispheres initially show three typical zones of
the neural tube:ventricular, intermediate, and
marginal; later a fourth one, the
subventricular zone, appears.
• Cells of the intermediate zone migrate into the
marginal zone and give rise to the cortical layers
• The gray matter is located peripherally, and
axons from its cell bodies pass centrally to form
the large volume of white matter (medullary
center).
37. • In the adult, a number of fiber bundles,
the commissures, which cross the
midline, connect the right and left
halves of the hemispheres.
Fig: Medial surface of the right half of the brain
in a 4-month embryo showing the various
commissures
38. • Once the neural plate is established, signals for segregation
of the brain into forebrain, midbrain, and hindbrain regions
are derived from homeogenes expressed in the notochord,
prechordal plate, and neural plate.
• The hindbrain has eight segments, the rhombomeres, that
have variable expression patterns of the Antennapedia class
of homeobox genes, the HOX genes . These genes are
expressed in overlapping (nested) patterns, with genes at the
most 3′ end of a cluster having more anterior boundaries
and paralogous genes having identical expression domains.
• Genes at the 3′ end are also expressed earlier than those at
the 5′ end, so that a temporal relation to the expression
pattern is established.
• Retinoids (retinoic acid) play a critical role in regulating
HOX expression. For example, excess retinoic acid shifts
HOX gene expression anteriorly and causes more cranial
rhombomeres to differentiate into more caudal types.
39. • At the neural plate stage, LIM1(prechordal plate) and OTX2 (neural plate) are
important for designating the forebrain and midbrain areas, with LIM1 supporting
OTX2 expression.
• Once the neural folds and pharyngeal arches appear, additional homeobox genes,
including OTX1, EMX1, and EMX2, are expressed in specific and in overlapping
(nested) patterns in the mid- and forebrain regions and specify the identity of
these areas. Once these boundaries are established, two additional organizing centers
appear: the anterior neural ridge (ANR) at the junction of the cranial border of the
neural plate and nonneural ectoderm and the isthmus between the hindbrain and
midbrain.
• In both locations, FGF8 is the key signaling molecule, inducing subsequent gene
expression that regulates differentiation. In the ANR at the four-somite stage, FGF8
induces expression of FOXG1 - then regulates development of the telencephalon
(cerebral hemispheres).
40. • In the isthmus -FGF8 induces expression of engrailed 1 and 2 (EN1and EN2), two
homeobox-containing genes, expressed in gradients radiating anteriorly and posteriorly
from the isthmus. EN1 regulates development of dorsal midbrain (tectum) and anterior
hindbrain (cerebellum), whereas EN2 is involved only in cerebellar development.
DORSOVENTAL PATTERNING IN FOREBRAIN AND MIDBRAIN:
• Ventral patterning is controlled by SHH secreted by prechordal plate induces
expression of NKX2.1 regulate development of hypothalamus.
• Dorsal patterning by BMP4 and BMP7 expressed in nonneural ectoderm adjacent to
neural plate.
• Induce expression of MSX1 in midline and repress expression of FOXG1.
• After neural tube closure BMP2 and BMP4 regulate expression of LHX2 in cortex.
41.
42. Diagram of the cranial neural plate region shown in A (blue area) illustrating the organizing center known as the anterior
neural ridge (ANR). This area lies in the most anterior region of the neural plate and secretes FGF8, which induces
expression of FOXG1 in adjacent neurectoderm. FOXG1 regulates development of the telencephalon (cerebral
hemispheres) and regional specification within the prosencephalon (PR). Sonic hedgehog (SHH),
secreted by the prechordal plate (P) and notochord (N), ventralizes the brain and induces expression of NKX2.1, which
regulates development of the hypothalamus. BPM4 and 7, secreted by the adjacent nonneural ectoderm, control dorsal
patterning of the brain. M, mesencephalon; R, rhombencephalon.
43. Time for Radical Changes in Brain Stem Nomenclature - Applying the Lessons From Developmental Gene
Patterns. "
The traditional subdivision of the brain stem into midbrain, pons, and medulla oblongata is based purely on the
external appearance of the human brain stem. There is an urgent need to update the names of brain stem structures to
be consistent with the discovery of rhomobomeric segmentation based on gene expression. The most important
mistakes are the belief that the pons occupies the upper half of the hindbrain, the failure to recognize the isthmus as
the first segment of the hindbrain, and the mistaken inclusion of diencephalic structures in the midbrain. The new
nomenclature will apply to all mammals. This essay recommends a new brain stem nomenclature based on
developmental gene expression, progeny analysis, and fate mapping."
PMID: 30809133 PMCID: PMC6380082 DOI: 10.3389/fnana.2019.00010
Molecular and cellular reorganization of neural circuits in the human lineage
To better understand the molecular and cellular differences in brain organization between human and nonhuman
primates, transcriptome sequencing of 16 regions of adult human, chimpanzee, and macaque brains was performed.
Integration with human single-cell transcriptomic data revealed global, regional, and cell-type-specific species
expression differences in genes representing distinct functional categories. Integrated analysis of the generated data
revealed diverse molecular and cellular features of the phylogenetic reorganization of the human brain across
multiple levels, with relevance for brain function and disease.
PMID: 29170230 PMCID: PMC5776074 DOI: 10.1126/science.aan3456
44. • Scientists have been fascinated by the human brain for
centuries, yet knowledge of the cellular and molecular
events that build the human brain during
embryogenesis and of how abnormalities in this
process lead to neurological disease remains very
superficial. Advances in stem cell–derived models of
human organogenesis, in the form of three-dimensional
organoid cultures, and transformative new analytic
technologies have opened new experimental pathways
for investigation of aspects of development, evolution,
and pathology of the human brain.
3D Brain Organoids: Studying
Brain Development and Disease
Outside the Embryo
Annual Review of Neuroscience
Vol. 43:375-389 (Volume publication
date July 2020)
https://doi.org/10.1146/annurev-neuro-
070918-050154
NEW
45. • The Five Faces of Notch Signalling During Drosophila melanogaster
Embryonic CNS Development
• During central nervous system (CNS) development, a complex series of events
play out, starting with the establishment of neural progenitor cells, followed by
their asymmetric division and formation of lineages and the differentiation of
neurons and glia. Studies in the Drosophila melanogaster embryonic CNS have
revealed that the Notch signal transduction pathway plays at least five different
and distinct roles during these events.
Notch Signaling in Embryology and Cancer. Advances in Experimental Medicine
and Biology, vol 1218. Springer, Cham. https://doi.org/10.1007/978-3-030-34436-8_3
46. Developmental Biology. 6th edition. Gilbert SF.
The Basics of Brain Development Neuropsychol Rev. 2010 Dec; 20(4): 327–348.PMCID:
PMC2989000
Multivitamin/folic acid supplementation in early pregnancy reduces the prevalence of neural tube
defects A Milunsky et al PMID: 2478730
Prevention of the first occurrence of neural-tube defects by periconceptional vitamin
supplementationA E Czeizel et al
Embryology of neural tube developmentT.W. Sadler First published: 01 April 2005
https://doi.org/10.1002/ajmg.c.30049
https://embryology.med.unsw.edu.au/embryology/index.php/Lecture_-_Neural_Development
Langman's Medical Embryology Author(s): T.W. Sadler
THE DEVELOPING HUMAN CLINICALLY ORIENTED EMBRYOLOGYMark G. Torchia, T.V.N.
(Vid) Persaud ,Keith L. Moore
Molecular and cellular reorganization of neural circuits in the human lineage