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CNS Development
- Embryogenesis
o Induction
o Neurulation
o Vesicle formation
o Ventricular system
o Choroid plexus
- Histogenesis
o Cellular differentiation (proliferation and migration)
o Cellular Maturation
Embryonic Period
rd th
- 3 to 8 Week
- Anything that will happen may cause major morphologic
abnormalities
Fetal Period
th
- 9 Week onward
- Functional defect and/or minor morphologic abnormalities
Ectoderm
- Neural ectoderm – CNS, PNS
- Surface ectorderm - Epidermis
- Neurocutaneous syndrome (Phakomatoses) – Skin
o Primary Neurulation
manifestation of a CNS problem
§ Process by which the brain and most (cervical,
thoracic, upper lumbar) of the spinal cord are
Mesoderm + Endoderm à other organs and organ systems formed
§ Begins when the notochord induces the overlying
EMBRYOGENESIS embryonic ectoderm to form a neural plate
th th
§ 17 to 18 day
Induction
§ Neural tube must be closed off from CSF
- Start of embryogenesis
§ Neural Crest Cells à PNS
- Process of cell to cell signaling to undergo changes
§ Neural Tube à CNS
- Underlying mesoderm induces the ectoderm to become the
§ Somites simultaneously grows with the neural tube
future neural ectoderm and form the neural plate, giving rise § Day 24 – Ant. Neuropore closure
to most of the nervous system § Day 26 – Post. Neuropore closure
- Takes place in the ectoderm of the head process overlying § Neural folds come together in the cervical region
the notochord and fuse; closure then proceeds in a rostral and
- Due to hormones, neurotransmitters, and growth factors caudal direction
th th
- 16 to 17 day
§ Requires folate (folic acid) for proper nervous
system development
Notochord
• Taken 1 month before conception and
- Directs the overlying ectoderm to form the neural plate
continuing through the first trimester
(neural ectoderm)
• For prophylaxis: 400 mcg (0.4 mg) / day
- Defines the longitudinal axis of the embryo (by production of
cell adhesion molecules) • For those with family history or a member who
- Determines the orientation of the vertebral column has history of spina bifida: 4000 mcg (4.0 mg) /
- Persists as the nucleus pulposus of the intervertebral disks day
• Cofactor in converting homocysteine to
methionine
NEUROSCIENCE 1 Neuroembryology – Edgardo Tan, MD
Telencephalic Flexure
th
At the end of the 5 week AOG:
- Telencephalon
o à Cerebral cortex and the subcortical while matter
(including internal capsule), the olfactory bulb and tract,
portions of the basal ganglia, the amygdala, and the
hippocampus
- Diencephalon
o à Thalamic nuclei and associated structures and also
to the optic cup (optic nerve and retina)
NEUROSCIENCE 1 Neuroembryology – Edgardo Tan, MD
Cavity inside the neural tube is forming during the vesicular Choroid Plexus Development
stages: - Responsible for CSF production
- Telencephalon à Hemisphere à 2 Lateral Ventricles - Develops in the floor and roof the lateral ventricle, and roofs
- Diencephalon à Third Ventricle (Interventricular Foramen of the third and fourth ventricles by a process of invagination
of Monro) of blood vessels
- Midbrain à Aqueduct of Sylvius (Iter) - Formed by a core of blood vessels surrounded by pia which
- Metencephalon à Pons and Cerebellum + is adherent to the ependymal lining of the vesicles
Myelencephalon (Medulla) à Fourth Ventricle - Develops where pia mater and ependymal are in direct
o Foramen of Magendie - Midline contact
o Foramen of Luschka - Lateral - Iter – no contact with Choroid Plexus
Somite Differentiation
- Cranial-to-caudal formation
- Day 20 to 35
- Sclerotome à Bone and cartilage
- Dermomyotome
o Dermatome à Dermis
o Myotome à Skeletal muscle
Three-Vesicle Five-Vesicle Adult Structure
Stage Stage (Maturation) Neural Ectoderm:
th
(4 Week)
th
(5 Week) - Neuroblastic – Forms neurons
Prosencephalon Cerebral 2 lateral - Glioblastic – Forms supporting cells (glial cells – hugs the
(Telencephalon hemisphere ventricles axons of the CNS for insulation)
and and Third Ventricle o Astrocytes
Diencephalon) diencephalon (Foramen of o Oligodendroglia
(Prososcele) 2 lateral telocele Monro) o Radial glial cells
Median telocele o Ependyma
Diocele
Mescencephalon Midbrain Aqueduct of Microglia – from mesoderm
(Midbrain) Mesocele Sylvius
(Mesoscele) (Iter) Neural Tube
Rhombencephalon Pons and Fourth Ventricle - Gives rise to the CNS
(Metencephalon cerebellum (Foramen of - Rostral 2/3 gives rise to the brain
and Medulla Magendie) - Caudal 1/3 gives rise to the spinal cord up to the lumbar
Myelencephalon) Metacele (Foramina of levels
(Rhombocele) Myelocele Luschka) - Caudal eminence gives rise to the sacral and coccygeal
segments
Abnormalities
- Congenital Hydrocephalus Neural Crest
o From birth - Gives rise to the PNS
o Congenital aqueductal atresia - Melanocytes
o Block of the iter - Schwann cells
- Dandy-Walker Malformation - CNs ganglia (5, 7, 9, 10)
o Poster fossa malformation - Autonomic ganglia (Postganglionic symp. neurons)
- Neurons and satellite cells of symp. ganglia
Defects of Prosencephalization - Dorsal root ganglia
- Prosencephalon (Forebrain) is developed with the facial - Arachnoid and pia mater (leptomeninges)
features - Adrenal medulla
- “The more sever the brain malformation, the more severe the - Chromaffin tissue
facial defect.”
- Holoprosencephaly - single-lobed brain HISTOGENESIS
o Alobar Holoprosencepaly – No corpus callosum
o Semilobar Holoprosencephaly – Incomplete forebrain - Cellular Differentiation
division - Cellular Migration and Maturation
o Reults from a failure of cleavage of the embryonic
prosencephalon by Day 35 Cellular Differentiation
o One telecephalon and one diencephalon - Radial glia – serve as transient cell guide for cell migration
- Environmental exposusres to alcohol, retinoic acid, and o Forms astrocytes after cell differentiation and migration
maternal diabetes - Three distinct layers:
- Syndromic disorders as Trisomy 13 and 18 o Ependymal or Ventricular Zone – most of the cells of
- Gene defects SHH 7q36 the neural tube multiplication happens here
- TORCH o Intermediate (Mantle) – primordia of future gray matter
- HIV o Marginal – primordia of future white matter
NEUROSCIENCE 1 Neuroembryology – Edgardo Tan, MD
NEUROSCIENCE 1 Neuroembryology – Edgardo Tan, MD
Midbrain – CN 1, 2 Diencephalon
Mesencephalon Midbrain - Hypothalamus
Neural Cavity à Sylvian Aqueduct of Iter - Thalamus
Alar Plate à Superior and Inferior Colliculus Nuclei o Outside First Sequence – Grows outside first
Red Nucleus o Radial glial cells grow up and down, some stay outside;
Substantia Nigra when folded there is a second layer, third layer
Basal Plate à Oculomotor Nucleus (GSE) o Geniculate ganglion develops first before the
Trochlear Nucleus (GSE) dorsomedial nuclei
Edinger-Westphal (EWpg) Nucleus o Orderly map of the sensory world
(GVE) § Lateral geniculate – part of the visual pathway
§ Medial geniculate – part of the auditory pathway
Rhombomeres § Ventral posterolateral nucleus – somatosensory
- Clusters of immature cells separated by thin bands of - Epithalamus – pineal gland, habenular nuclei, stria
neuroepithetial cells medullaris
- Segmentation and regionalization
- 8 segments: Each rhombomere has assigned part
o r1 – Mesencephalon
o r8 – Medulla
- Genes that will the
neural tissues in that
area that they are
confined in that
segment
- Neuromeres –
located at the spinal
canal
Metencephalon
- Develops into 2
structures
- Pons and cerebellum
Cerebellum
Development
- Derivative of metencephalon
- Thick area of Rhombomere 3 (r3) à Cerebellum
o Divides and grow; Produces lots of infoldings to
accommodate the fast growing
- Cerebellum – important for coordination of motor cells
- Postero-lateral Fissure
o Forms first
o Divides tissues into flocculonodular lobe and cerebral
Cerebral Hemisphere
body of the cerebellum body
- Inside-Out Pattern
- Primary Fissure
o First grows inside, then goes outward; Folding à 6
o Divides cerebellum body into anterior and posterior
layers
lobes
o Oldest layer: Layer 1
- Neurons of the cerebellum are derived from neuroblasts in
o First wave: Layer 6
the ventricular zone of the cerebellar primordium forming the
o First cells to migrate disembark and take positions close
deep cerebellar nuclei (responsible for the coordination of
to ventricular surface
movement: lateral à Dentate, Emboliform, Globose,
- Early development of the cerebral cortex
Fastigii ß medial) and the Purkinje and Golgi Cells
o The nuclei of the neuroblasts undergo a cycle of
- Three layers
outward and inward migration as the neuroblasts
o Molecular layer
progress through their cell cycle (G1 – first gap phase; S
o Purkinje layer
– DNA replication; G2 – second gap phase; M – mitosis
o Granular layer
and cytokinesis)
- Outside-In pattern – grows outside, then goes inside
Formation of the Cerebral Cortex
- All of them comes from the cortical plate
- Formation of cortical plate at interface of marginal zone and
intermediate zone
- Formation of subplate – a narrow region internal to cortical
plate
- Marginal zone gives rise to layer 1
- Cortical plate gives rise to layers 2-6
- Subplate and intermediate zone (internal cortical plate)
give to subcortical white matter
NEUROSCIENCE 1 Neuroembryology – Edgardo Tan, MD