NEUR3005 – Semester 1
Be familiar with the major cellular building blocks of the central nervous system
Neurons – Derived from Neural Stem cells
• 100 billion neurons (but only make up only 10% of all brain cells)
• Most neuronal proliferation in first 5 mths
• Most neuronal differentiation 4-9 mths
• Neuronal connections continue to form postnatally (after birth)
Glial cells (“glue”) Function
Astrocytes • Homeostatic functions (recycle glutamate) + responds to injury
• Structural support of brain
• Contribute to BBB
Oligodendrocytes Myelination of axons for faster conduction (occurs postnatally)
Microglia • Resident immune cells of CNS phagocytosis + response to injury
o At rest = many mobile processes that survey area
o Active = few processes to complete phagocytosis
Ependymal cells • Line ventricles and choroid plexus
• Produce CSF
*Glial cells (except microglia) are derived from neural stem cells but differentiate later than neurons
Be familiar with the development timeline of: the neural tube, primary and secondary vesicles, the
ventricular system, the telencephalon, cerebral convolutions and white matter
• Neurons are derived from the ectoderm (outer layer of trilaminar embryo)
Formation of the neural • Midline mesoderm releases signalling molecules which lead to thickening of the
rd
groove (3 week) overlying ectoderm to form the neural plate
• Neural plates folds inwards to form the neural groove
Primary neurulation and • Neural tube closes (Day 20-26) + detaches from the ectodermal surface (the skin)
formation of the primary o Day 24: Rostral end closes brain
th
vesicles (4 week)
o Day 26: Caudal end closes spinal cord
• Remaining neural crest cells form peripheral nervous system (e.g. dorsal root
ganglion, glial cells)
Neural tube defects
• Failure of the rostral end of the neural tube to close =
catastrophic developmental defect (miscarriage)
• Failure of the caudal end of the neural tube to close =
spina bifida
,Understand the origins of dorsal/ventral (spinal cord) versus medial/lateral (metencephalon)
organisation of sensory and motor systems
Dorsal-ventral patterns of differentiation
• Ectoderm next to the neural plate produces an opposing signalling molecule bone morphogenetic proteins (BMPs)
o Differentiation into sensory neurons
• Midline mesoderm (and later the notochord) releases a signalling molecule called sonic hedgehog (SHH)
o differentiation into motor neurons
Alar plate vs. basal plate derivatives
• Different morphological gradients of signalling
molecules establish a functional organisation, which
persists in the adult spinal cord
• Alar (dorsal) derivatives = become sensory neurons
• Basal (ventral) derivatives = become motor
neurons
Understand the gene patterning which drives rostrocaudal organisation of rhombomeres
• FGF8 and Retinoic acid (RA) concentration gradient establishes a rostral – caudal orientation that different
rhombomeres to have different patterns of development (give rise to different cranial nerves)
Development of parts of brain
Notochord closes to form primary vesicles forms 3 Secondary vesicles develop from:
parts: 1. Prosencephalon telencephalon, diencephlaon
1. Prosencephalon 2. Mesencephalon midbrain (no change)
2. Mesencephalon
3. Rhombencephlon metencephalon, mylencephlon
3. Rhombencephlon
,Pontine flexure (formation of 4th ventricle)
• The neural tube spreads apart to form a diamond- shaped cavity, with a thin membrane roof
• The opening of the neural tube causes the:
o Dorsal (sensory) /ventral (motor) orientation in the spinal cord becomes lateral (sensory) / medial
(motor) in the brain stem
• Sulcus limitans persists as an important boundary
Shaping the telencephalon (wks 6-12)
• Rostral tip of the neural tube forms a thin membrane called “lamina terminalis”
• Lamina terminalis is the origin of the bridge between the two hemispheres where bundles of interconnecting fibres
begin to grow (e.g. corpus callosum and anterior commissure)
o Basal part of the telencephalon thickens form pre-cursor of the basal ganglia
o Diencephalon thickens form thalamus and hypothalamus, separated by hypothalamic sulcus
rd
• END of 3 month = diencephalon and telencephalon have fused
Formation of temporal and frontal lobes
• Each cerebral hemisphere assumes the shape of a great arc
around the insula forms insular lobe
o Insular cortex grows slower
• Parts of the hemisphere originally dorsal to the insula get
pushed around into the temporal lobe (i.e. the hippocampus)
• Sulci (fissures) + gyri (folds) are convolusions to increase SA of
brain
Progressive development of cortical convolutions Continued growth of the telencephalon
(age in weeks) Further rapid growth leads to the insula cortex being overgrown
by the frontal, parietal and temporal lobes
, Cavity of the neural tube becomes the ventricular system
Understand the processes of cell proliferation, migration and differentiation
Neuronal Proliferation (peak 5wks 5mths)
• Proliferation of neuroblasts
o Occurs in ventricular zone
• Cleavage plane during cell division determines fate
• Vertical cleavage (early) = increased proliferation capacity
Notch-1 cell migrates away and stops division while Numb cell
• Horizontal cleavage (late) = reduced proliferation as one
continues to divide
daughter cell migrates to pia surface as lacking Numb gene
Note: Numb usually inhibits Notch-1
Migration
Inside-Out’ development of the cortex
• Neuroblasts cross the subplate to arrive in the cortical plate
st
(1 cells become layer VI neurons)
o Subplate disappears
• Radial glial cells: Provide scaffold on which cortex is built to
help neuroblasts migrate along their thin fibres to the pia 6 layers of neuraon in adult cerebral cortex (VI → I)
surface
Differentiation
• Neuroblasts differentiate into a neuron of a specific
phenotype
• Differentiation of astrocytes peaks at birth
• Differentiation of Oligodendrocytes postnatal
Postnatal production of myelin (T2 weighted MRI
CSF=bright/Myelin=dark)
• Most myelination occurs post-natally (along with synaptic
connections)
• Black areas of internal capsule, corpus callosum and cortex
appear more myelinated as baby ages
Be familiar with the major cellular building blocks of the central nervous system
Neurons – Derived from Neural Stem cells
• 100 billion neurons (but only make up only 10% of all brain cells)
• Most neuronal proliferation in first 5 mths
• Most neuronal differentiation 4-9 mths
• Neuronal connections continue to form postnatally (after birth)
Glial cells (“glue”) Function
Astrocytes • Homeostatic functions (recycle glutamate) + responds to injury
• Structural support of brain
• Contribute to BBB
Oligodendrocytes Myelination of axons for faster conduction (occurs postnatally)
Microglia • Resident immune cells of CNS phagocytosis + response to injury
o At rest = many mobile processes that survey area
o Active = few processes to complete phagocytosis
Ependymal cells • Line ventricles and choroid plexus
• Produce CSF
*Glial cells (except microglia) are derived from neural stem cells but differentiate later than neurons
Be familiar with the development timeline of: the neural tube, primary and secondary vesicles, the
ventricular system, the telencephalon, cerebral convolutions and white matter
• Neurons are derived from the ectoderm (outer layer of trilaminar embryo)
Formation of the neural • Midline mesoderm releases signalling molecules which lead to thickening of the
rd
groove (3 week) overlying ectoderm to form the neural plate
• Neural plates folds inwards to form the neural groove
Primary neurulation and • Neural tube closes (Day 20-26) + detaches from the ectodermal surface (the skin)
formation of the primary o Day 24: Rostral end closes brain
th
vesicles (4 week)
o Day 26: Caudal end closes spinal cord
• Remaining neural crest cells form peripheral nervous system (e.g. dorsal root
ganglion, glial cells)
Neural tube defects
• Failure of the rostral end of the neural tube to close =
catastrophic developmental defect (miscarriage)
• Failure of the caudal end of the neural tube to close =
spina bifida
,Understand the origins of dorsal/ventral (spinal cord) versus medial/lateral (metencephalon)
organisation of sensory and motor systems
Dorsal-ventral patterns of differentiation
• Ectoderm next to the neural plate produces an opposing signalling molecule bone morphogenetic proteins (BMPs)
o Differentiation into sensory neurons
• Midline mesoderm (and later the notochord) releases a signalling molecule called sonic hedgehog (SHH)
o differentiation into motor neurons
Alar plate vs. basal plate derivatives
• Different morphological gradients of signalling
molecules establish a functional organisation, which
persists in the adult spinal cord
• Alar (dorsal) derivatives = become sensory neurons
• Basal (ventral) derivatives = become motor
neurons
Understand the gene patterning which drives rostrocaudal organisation of rhombomeres
• FGF8 and Retinoic acid (RA) concentration gradient establishes a rostral – caudal orientation that different
rhombomeres to have different patterns of development (give rise to different cranial nerves)
Development of parts of brain
Notochord closes to form primary vesicles forms 3 Secondary vesicles develop from:
parts: 1. Prosencephalon telencephalon, diencephlaon
1. Prosencephalon 2. Mesencephalon midbrain (no change)
2. Mesencephalon
3. Rhombencephlon metencephalon, mylencephlon
3. Rhombencephlon
,Pontine flexure (formation of 4th ventricle)
• The neural tube spreads apart to form a diamond- shaped cavity, with a thin membrane roof
• The opening of the neural tube causes the:
o Dorsal (sensory) /ventral (motor) orientation in the spinal cord becomes lateral (sensory) / medial
(motor) in the brain stem
• Sulcus limitans persists as an important boundary
Shaping the telencephalon (wks 6-12)
• Rostral tip of the neural tube forms a thin membrane called “lamina terminalis”
• Lamina terminalis is the origin of the bridge between the two hemispheres where bundles of interconnecting fibres
begin to grow (e.g. corpus callosum and anterior commissure)
o Basal part of the telencephalon thickens form pre-cursor of the basal ganglia
o Diencephalon thickens form thalamus and hypothalamus, separated by hypothalamic sulcus
rd
• END of 3 month = diencephalon and telencephalon have fused
Formation of temporal and frontal lobes
• Each cerebral hemisphere assumes the shape of a great arc
around the insula forms insular lobe
o Insular cortex grows slower
• Parts of the hemisphere originally dorsal to the insula get
pushed around into the temporal lobe (i.e. the hippocampus)
• Sulci (fissures) + gyri (folds) are convolusions to increase SA of
brain
Progressive development of cortical convolutions Continued growth of the telencephalon
(age in weeks) Further rapid growth leads to the insula cortex being overgrown
by the frontal, parietal and temporal lobes
, Cavity of the neural tube becomes the ventricular system
Understand the processes of cell proliferation, migration and differentiation
Neuronal Proliferation (peak 5wks 5mths)
• Proliferation of neuroblasts
o Occurs in ventricular zone
• Cleavage plane during cell division determines fate
• Vertical cleavage (early) = increased proliferation capacity
Notch-1 cell migrates away and stops division while Numb cell
• Horizontal cleavage (late) = reduced proliferation as one
continues to divide
daughter cell migrates to pia surface as lacking Numb gene
Note: Numb usually inhibits Notch-1
Migration
Inside-Out’ development of the cortex
• Neuroblasts cross the subplate to arrive in the cortical plate
st
(1 cells become layer VI neurons)
o Subplate disappears
• Radial glial cells: Provide scaffold on which cortex is built to
help neuroblasts migrate along their thin fibres to the pia 6 layers of neuraon in adult cerebral cortex (VI → I)
surface
Differentiation
• Neuroblasts differentiate into a neuron of a specific
phenotype
• Differentiation of astrocytes peaks at birth
• Differentiation of Oligodendrocytes postnatal
Postnatal production of myelin (T2 weighted MRI
CSF=bright/Myelin=dark)
• Most myelination occurs post-natally (along with synaptic
connections)
• Black areas of internal capsule, corpus callosum and cortex
appear more myelinated as baby ages
