Embryology Flashcards by Briana Tillman

developmental organization of the CNS- major events

neurulation- 0-4 weeks
neuronal proliferation- 4-12 weeks
neural migration- 12-26
apoptosis- 16 weeks- childhood
synaptogenesis- week 18 through adolescence
myelination- week 28 through adulthood

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Most neuronal production and migration occurs

during the third through fifth months of development

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Neurulation

Neural tube formation

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Neuronal Proliferation

Mitotic division and fate determination

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Neural Migration

Axonal growth cones navigate to target synapses

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Synaptogenesis and apoptosis

Synaptic machinery is formed at synapses, unused synapses die off

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Myelination

Mature neurons are myelinated by oligodendrocytes

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Gliogenesis

takes place during the second and third trimesters of pregnancy and early postnatal development

Glia outnumber neurons 10:1 in the fully developed brain

Glial abnormalities related to Alzheimer’s, Multiple Sclerosis, Schizophrenia, Depression

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Morphogen

a signal produced from a defined localized source forms a concentration gradient as it spreads through surrounding tissue. The graded signal then acts directly on cells, in a concentration-dependent manner, to specify gene expression changes and cell fate selection.

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notochord’s job

The presence of the notochord is required for the formation of the neural plate from overlying ectoderm. Spemann organizer blocks ectodermal cells from making each other become epidermis

BMP- bone morphogenic protein

Noggin- blocks the effects of BMP –> nervous tissue default

notochord eventually becomes nucleus pulposus (mesoderm derived)

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Steps of neurulation

1) Formation of a neural plate
2) Neural plate becomes neural groove surrounded by crests
3) Groove becomes closed neural tube in highly ordered fashion

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neural tube closure defects

Craniorachischisis

Spina Bifida
- spina bifida occulta (doesn’t look like it didn’t close… tuft of hair)
- Mengingocele (Protrusion of dura and arachnoid)
- Meningomyelocele (Meningocele + spinal cord and nerves protruding (most common)
- Syringomyelocele - syrin is a cyst in the spinal cord (Meningomyelocele + central canal of spinal cord is distended) (most rare)
Anencephaly - not a viable fetus
Encephalocele - herniation of brain

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Factors in neural tube defects

Neural Tube Defects often related to elevated levels of alpha-fetoprotein
Folic Acid levels need to be sufficient to allow for proper neural tube closure

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when would the neural tube defects happen?

week 3– neural groove and folds, 3 primary vesicles visible, cervical and cephalic flexures, motor neurons appear

week 4- neural tube starts to close (day 22), rostral end of neural tube closes (day 24), cuadal end of neural tube closes (day 26), neural crest cells begin to migrate. Secondary neurulation starts, motor nerves emerge.

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rostral vs caudal neural tube defects

rostral- anencephaly and encephalocele

caudal- spina bifida

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difference between anencephaly and microcephaly

: Anencephaly differs from microcephaly in that anencephaly lacks major structures and is a neural tube defect, whereas microcephaly involves having the major neural structures ,but smaller, and it is a cortical development defect

3 vesicles of the neural tube

The neural tube is the central nervous system
3 Vesicles develop into the future brain
- prosencephalon (forebrain)
- mesencephalon (midbrain)
- rhombencephalon (hindbrain)

1st flexures

3 Bulges = “primary vesicles”
Cephalic flexure bet. Mesencephalon and prosencephalon
Cervical flexure bet. Rhombencephalon and spinal cord

2 more bulges –> 5 secondary vesicles

Rhombencephalon sep. to metencephalon and myelencephalon at level of pontine flexure

Prosencephalon sep. to diencephalon and telencephalon

Holoprosencephaly

Holoprosencephaly results from incomplete division of the prosencephalon. There are many causes, including problems with the morphogen SHH (sonic hedgehog)

problems with the midline (from eye asymmetry to cyclops)

Embryonic derivatives of the 3 primary vesicles

Prosencephalon–> telencephalon –> cerebral cortex, basal ganglia

prosencephalon –> diencephalon –> thalamus, hypothalamus, retina

mesencephalon–> mesencephalon –> midbrain

rhombencephalon–> metencephalon–> cerebellum, pons

rhombencephalon–> myelencephalon–> medulla

lumen of neural tube becomes…

ventricular system.

Each vesicle contains different “ventricle”

c shape emerges wehre?

around the insula

Common disorders of migration

microgyria
lissencephaly
microcephaly
schizencephaly

microgyria

excess sulcation

lissencephaly

smooth brain

microcephaly

reduced brain size, reduced head size

schizencephaly

clefts in cerebral hemispheres

Two signaling systems pattern the dorsoventral axis

``` Sonic hedgehog (Shh) = secreted signaling molecule; initially expressed in the notochord (N) Bone morphogenetic proteins (BMPs) = secreted signaling proteins with a variety of functions; expressed in ectoderm (ECT) ``` Early dorsal ventral patterning starts while the nervous system is still a flat structure (I.e. the neural tube hasn’t even formed yet). At this point, the patterning signals come in two flavors - lateral signaling from the BMPs in the ectoderm and planar signaling from sonic hedgehog in the notochord. These two signaling systems are setting up the parameters of dorsal-ventral patterning before the anatomic axes are even established. At this stage, neither of the signals is actually expressed within the nervous system.

floorplate vs epidermis

``` Shh = ventral; expressed in notochord and floorplate (F) BMPs = dorsal; expressed in epidermis ``` As the neural tube begins to fold, Shh expression begins in the floorplate (within the nervous system). BMPs continue to be expressed in the epidermis ``` Shh = ventral; expressed in notochord and floorplate BMPs = dorsal; expressed roofplate (R) Neural crest (NC) delaminates at this stage ``` Once the neural tube is closed, the roofplate expresses one signal and the floorplate expresses a second signal. These signals are responsible for patterning dorsal and ventral regions of the spinal cord, respectively.

the fate of the marginal, mantle, and ependymal cells

Mantle zone becomes gray matter, marginal zone becomes white matter. Neurons start out in the ependymal zone (also known as the ventricular zone). Mantle zone is also known as the intermediate zone. Ependymal zone becomes less populated as neurons move out. Use this to desribe how you work your way out.

neurogenesis

Progenitors become radial glia and then can develop into either neurons or glia

Formation of brain stem: metencephalon

Metencephalon is formed in two divisions: Dorsal division looks like medulla Alar plate forms cerebellum 1. Develops from Rhombic Lip Sensory Cranial Nuclei (V) 2) Ventral division, basal pons contains pontine nuclei. This doesn’t follow typical dorso-ventral patterning

Formation of the brain stem: mesencephalon

Tectum Alar plate of the mesencephalon forms the corpora quadrigemina (Inferior colliculi and Superior colliculi) GSA of CN V is another alar-derived nucleus Tegmentum Basal plate of the mesencephalon forms GSE and GVE of CN III GSE of CN IV

Formation of the diencephalon

Alar plate is largely thalamus Basal plate is largely hypothalamus Roof and alar plates give rise to epithalamus (habenula and pineal) Optic cup, another derivative, becomes CN II

Formation of the Telencephalon takes place in 2 waves

Initial pattern of gray and white matter development is similar to that of the rest of the neural tube. The neocortex (or neopallium) undergoes a second pattern of development to allow for many layers (6)

Neural crest cells have a different fate than neural tube cells

Neural crest forms the majority of the peripheral nervous system: ``` Autonomic Ganglia Spinal nerves Schwann cells Melanocytes Adrenal medullary cells Pia Arachnoid Tendons of facial musculature ```

Choroid plexus is

vascular tissue + pia + ependymal cells Makes CSF Not in aqueduct nor spinal cord