Brain Structure: Developmental Perspective (2)

neural plate/tube becomes…

CNS

4 divisions of CNS that develop

prosencephalon, mesencephalon, rhombencephalon, caudal neural tube

prosencephalon becomes…

forebrain of diencephalon and telencephalon

mesencephalon becomes…

midbrain

rhombencephalon becomes…

hindbrain of cerebellum and brainstem (pons, medulla)

caudal neural tube becomes…

spinal cord

4 steps of CNS development and generally what happens

1) induction on neural plate → flat tissue becomes neural plate

2) neurulation → formation of neural tube from neural plate tissue due to induction signals (partly from notocord)

3) neural tube patterning → regions of brain begin to form due to morphogens

4) proliferation, differentiation, and migration → regions grow and produce neurons, which then differentiate and travel to correct location

PNS forms from…

neural crest → produces glial cells & PNS neurons, glial cells wrap around neurons

3 germinal layers of embryos & what they will become

inner: endoderm → internal organs

mesoderm → bones & muscle

outer: ectoderm → skin & nervous system

germinal layer from which the CNS & PNS

dorsal ectoderm layer → neural plate → neural ectoderm → CNS

most dorsal part of neural folds/closing neural tube → neural crest → PNS (& cell bodies for other tissues)

two steps of neurulation and generally what happens

1) primary neurulation → neural plate becomes neural tube, which forms brain and spinal cord up to lumbar level

2) secondary neurulation → caudal eminence forms, sacral & coccygeal (lower) spinal cord segments form

4 steps of primary neurulation

1) elongation

2) folding

3) convergence

4) closure

elongation in primary neurulation

neural plate cells proliferate and grow; neural plate starts to bend at medial hinge and form neural groove

medial hinge point

where neural plate starts to bend in primary neurulation, forming the neural groove and allowing vertical growth

folding in primary neurulation

neural folds (vertical halves of neural plate) elevate and approach the neural crest (border tissue continuous with ectoderm), folding towards the dorsal midline

convergence in primary neurulation

dorsolateral hinge points (DLHP) let neural folds bend inwards to converage at the top of the newly formed tube

closure in primary neurulation

neural folds fuse and the neural crest laminates, connecting the folded neural plate into the neural tube

how does closure in primary neurulation work?

neural folds first connect at closure points, then closure extends from those like a zipper

the anterior neuropore closes before posterior neuropore

~ time after conception for primary neurulation folding

18 days

~ time after conception for primary neurulation closure, anterior & posterior neuropores

anterior: 24 days

posterior: 26-28 days

anencephaly definition & how it occurs

embryo lacks a brain; occurs if anterior neuropore doesn’t close in primary neurulation

spina bifida definition & how it occurs

spine condition where the spinal cord never fully closes; occurs if posterior neuropore doesn’t close in primary neurulation

neural tube defects, like anecephaly or spina bifida, are known as…

dysraphic defects

secondary neurulation forms

caudal eminence, which fuses with the neural tube at the end (AKA tail bud but we don’t get tails)

saccral & coccygeal spinal cord segments → below lumbar region that primary neurulation stops at

defects in secondary neurulation will cause…

loss of leg/feet sensation, loss of bladder control (lower spinal cord is responsible for these functions)

~ time after conception that secondary neurulation occurs

5-6 weeks

2 steps of neural tube patterning, generally what happens

1) dorsal-ventral & rostro-caudal patterning (which coincides with neurulation) due to morphogen gradients

2) segmentation of neural tube (morphogens, organizers)

morphogens are…

signaling molecules released from different tissues that spread/diffuse, creating a concentration gradient. exposure to various amounts of gradients determines the identity/fate of cells, which helps create brain regions of specific types of progenitors → neurons from various neural tube territories

2 most important dorsal-ventral patterning morphogens & their effects

SHH (sonic hedgehog), ventralizing effect

BMPs (bone morphogenic proteins), dorsalizing effect

SHH stimulates creation of…

ventral neural tube → Basal plate → motor

BMPs stimulates creation of…

dorsal neural tube → Alar plate → sensory

what is the sulcus limitans & why does it form

structure forming between Basal and Alar plates where the two morphogen-caused gradients balance/cancel out, since SHH and BMPs are antagonistic signals and cannot overlap

rostral end of neural tube forms…

entire encephalon (brain)

caudal end of neural tube forms…

spinal cord

2 main steps of rostro-caudal patterning differentiation

1) 3 primary vesicles form in anterior neural tube

2) 5 secondary vesicles form

primary vesicles in rostro-caudal patterning, what they become

prosencephalon (forebrain)

mesencephalon (midbrain)

rhombencephalon (hindbrain)

~ time after conception that primary vesicles form in rostro-caudal patterning

4 weeks

secondary vesicles in rostro-caudal patterning, where they come from, what they become

prosencephalon → 2 telencephalic vesicles, diencephalon, also optic vesicles (optic stalk & cups, will become optic nerve and retina)

mesencephalon stays as-is

rhombencephalon → metencephalon (→ pons, cerebellum) & myelencephalon (→ medulla)

morphogens in rostro-caudal patterning & impact

larger variety of morphogen gradients that define distinct territories of gene expression, which become different vesicles

some morphogens: FGFs, Wnt, Retinoic Acid

~ time after conception of rostro-caudal secondary vesicle formation

8 weeks

what proliferation, differentiation, and migration mean generally

proliferation: progenitors divide and create more progenitors

differentiation: progenitors become different types of neurons upon terminal division (diff progenitors impacted by morphogens = diff neurons)

migration: different neurons migrate to appropriate final locations

where does progenitor proliferation occur

in germinal zone, creating the neuroepithelium

form neural tube wall and line neural canal (tube lumen)

terminal division, what happens

progenitors divide a last time into a specific type of neuron (determined by morphogen type and ‘dosage’ that that progenitor was exposed to), which will not re-enter the mitotic cycle and will migrate from germinal zone

how do newly formed neurons migrate out of germinal zone

radial glia progenitors become radial scaffold upon which neurons can travel

pathway of morphogen → different brain structures

morphogen type & ‘dosage’ → differently expressed transcription factors in progenitors → different progenitor fates → different types of cells/neurons → different distinct brain structures

2 important dorso-ventral neuron lineages → CNS

dorsalizing effect of morphogens (BMPs) → Alar plate formation → Alar progenitors → neurons for sensory structures

ventralizing effect of morphogens (SHH) → Basal plate formation → neurons for effector/motor structures

spinal cord gray matter final structures

dorsal horns, ventral horns, made of neurons derived from Alar & Basal plates

spinal cord white matter final structures

surrounds gray matter, made of fibers, includes dorsal, lateral, and ventral columns

derivation of dorsal horns

Alar plate → sensory neurons → dorsal horns (gray matter)

derivation of ventral horns

Basal plate → motor neurons → ventral horns (gray matter)

embryonic CNS structures (side view)

blue: forebrain

red: midbrain

green: hindbrain

yellow: caudal neural tube

embryonic & postnatal CNS structures (front view)

blue: forebrain

red: midbrain

green: hindbrain

yellow: caudal neural tube

embryonic spinal cord cross section, label

developed/postnatal spinal cord cross section, label

derived/differentiated hindbrain structure

rhombencephalon, including medulla, pons, cerebellum

maintains tube-like shape (along with spinal cord)

alar plate is dorsal to sulcus limitans, basal plate is ventral

alar plate derivatives are…

afferent/sensory

basal plate derivatives are…

efferent/motor

alar plate derivatives present in developed/differentiated hindbrain

special somatic afferent (SSA)

general visceral afferent (GVA)

special visceral afferent (SVA)

general somatic afferent (GSA)

basal plate derivatives in developed/differentiated hindbrain

general somatic efferent (GSE)

general visceral efferent (GVE)

special visceral efferent (SVE)

alar plate derivatives in developed/differentiated spinal cord

general visceral afferent (GVA)

general somatic afferent (GSA)

basal plate derivatives in developed/differentiated spinal cord

general somatic efferent (GSE)

general visceral efferent (GVE)

developed hindbrain cross section (dorsal - ventral), label

developed hindbrain & spinal cord cross sections (rostro-caudal) label

the myencephalon differentiates into…

caudal rhombencephalon (medulla)

mature medullas have…

ascending and descending axon bundles, alar and basal plate derivatives, pyramids of medulla

function of asc/desc axon bundles in mature medullas

connect spinal cord and other CNS structures

alar plate derivatives in mature medulla

somatic sensory nuclei, visceral sensory nuclei

basal plate derivatives in mature medulla

visceral motor nuclei

what happens with/what are pyramids of mature medulla

motor axons desc from cerebral cortex and cross midline (decussate) in pyramidal decussation (which is border bw spinal cord and medulla)

labeled mature medulla (myelencephalon diff)

the metencephalon differentiates into…

rostral rhombencephalon

characteristics of mature rhombencephalon

pons, cerebellum, rhombic lips

rhombic lips location, become

dorso-lateral position of metencephalon, grow dorsally to form cerebellum

motor axons from cortex synapse in __ and project to __

pons, cerebellum

alar plate derivatives in mature rhombencephalon

sensory nuclei of cranial nerves in cerebellum

basal plate derivatives in mature rhombencephalon

motor nuclei of cranial nerves in pons

why is it difficult to distinguish alar and basal plate derivatives in the mature prosencephalon, especially telencephalon & current hypothesis

very complex morphogen gradients and extensive cell migrations; very active research field → seems that almost all telencephalic structures are consistent with being alar plate derivatives

alar plate derivatives in diencephalon

alar plate deriv → thalamus

basal plate derivatives in diencephalon

basal plate deriv → hypothalamus

di/telencephalon label

label

telencephalic vesicles, form

medial pallium → hippocampus

dorsal pallium → cerebral cortex

lateral pallium → amygdala, piriform cortex

ventral pallium → amygdala

LGE, MGE → subpallium → basal ganglia

dorsal pallium becomes

cerebral cortex (telencephalic diff)

dorsal pallium growth compared to other telencephalic vesicle sections?

disproportionate → expands until all available space in the skull is occupied, folding in on itself to pack more cortical tissue into limited space

telencephalic growth direction, shape

all directions but primarily dorsally & caudally, becomes a C shape due to bending and expansion of dorsal pallium within limited skull space

ganglionic eminence becomes, location

basal ganglia, stays in telencephalon core

telencephalon hollow space becomes

lateral ventricles (part of ventricular system