In the cerebral cortex, the first neurons to become postmitotic migrate to form a new region known as the _____.
22. Define radial, tangential and chain migration and identify what class of neurons undergoes radial migration, tangential migration, and chain migration.
- radial = majority of migration; clusters of cells; ride radial glia
- tangential = dispersion throughout tissue; paths are inhibitory GABA-containing cells
- chain = neurons from subventricular zone to the olfactory bulb; no glial cells; move in chains in rostral migratory stream
When the plane of cleavage is parallel to the ventricular surface, ______. This is called asymmetrical division.
one of the daughter cells remains attached but the other does not
12. Provide examples of long‐range and short‐range axon guidance molecules and identify which are attractive or repulsive.
- long range = diffusion
- short range = direct contact
- attractive = netrins (long range); cadherins, CAMs, collagin, laminin, fibronectin, and proteoglycans (short range)
- repulsive = semaphorins, netrins (long range); semaphorins, ephrins, tenascin (short range)
How many neurons are in the human CNS? Glial cells?
While _____, the nucleus is located most deep.
cellular division occurs (M phase, mitosis)
While _____, the nucleus is located most superficially.
DNA is being synthesized (S phase)
13. Define and describe what are neurotrophins and the roles they play in neuronal development.
neutrophins = induce differentiations, formations of processes can either attract or repel the growth cone over long distances (diffusible) or short distances (contact dependent)
18. Describe the role that radial glia play in neuronal migration.
Radial glia extend from the ventricle to the surface and serve as guides during neuronal migration. They are like a scaffold.
4. Identify which brain regions are areas of secondary neurogenesis.
- Cerebellum (external granule layer)
- Olfactory system (subventricular zone)
- hippocampus (dentate gyrus)
When a progenitor cell in the ventricular zone divides, the plane of cleavage can be either _____ or ______.
perpendicular or parallel
The neuroectoderm rounds up and forms the ____.
When the plane of cleavage is ______ to the ventricular surface, both daughter cells remain attached to the ventricular surface and the cells _____ in the cell cycle.
19. For both the cerebral cortex and retina, describe where the first‐born cells are found with respect to the ventricular zone.
- cerebral cortex= first born medial and later born to periphery (inside-out)
- retina = ganglion cells born first and photoreceptors last (outside-in)
25. Compare and contrast "apoptosis" with "necrosis."
- apoptosis = programmed cell death; cell shrinks and is eventually cleared by macrophages
- necrosis = accidental cell death; cell contents spill
What happens to the subplate neurons?
most die after their pioneering roles play out
In the cerebral cortex, specialized glia called ______ extend from the ventricle to the surface and are used as guides during migration.
15. Define synapse elimination and discuss when and where it occurs.
synapse elimination = removal of excess nerve contacts ex: muscles are innervated by multiple motor neurons during development/early postnatal life, but this is then reduced by retraction of some individual motor neurons
Neurons migrate into the cortical plate using ______ as a scaffold.
Once a cell _____, it leaves the ventricular zone.
leaves the mitotic cycle
When does the majority of neurogenesis occur?
3. Describe when myelination occurs.
- begins during embryonic stages
- first present in periphery
- CNS = spinal cord @ end of 1st trimester, brain by end of 3rd trimester, cortical tracts after birth
24. Contrast migration of neural crest cells to radial migration in the cerebral cortex.
- neural crest cell migration = from top of the dorsal neural tube throughout the body
- dorsal stream migration or ventral stream migration
- laminin and fibronectin involved radial migration = inside-out pattern
What region of the hippocampus develops postnatally?
Proliferating cells are found in the _____.
1. Describe factors/mechanisms that determine when a cell stops dividing and begins differentiating.
- Keep dividing= stay attached to ventricular surface; signaling factors inhibit division
- Stop dividing and differentiate = detach from vent. surface; signaling factors keep it dividing
What region of the olfactory system develops postnatally?
the subventricular zone
7. Describe the changes in nuclear position that occur during the cell cycle of neuronal precursors.
- nucleus superficial (near pial surface) = S phase (DNA replication)
- nucleus deep (near ventricular surface) = M phase (mitosis)
- nucleus intermediate = G1, G2 (gap)
6. Describe methods used to study neurogenesis.
Use radiolabeled nucleotides to track replication and cell division
11. Identify factors that influence the ability of axons to regenerate.
- ability to grow
- presence of growth factors (FGF, neutrophins)
- presence of molecules/receptors that inhibit growth (Nogo)
20. Describe genes that play a role in neuronal migration in the cerebral cortex and which stages of migration they affect.
- Reeler = inside-out pattern of cortical organization; mutant = inversion *** step 1 (onset) and step 3 (stopping)
- filaminA gene (FLNA) = actin binding crosslinking protein; mutations cause periventricular heterotopia (PH) *** step 1 (onset)
- LIS1 = helps migration towards cortical plate; mutation = smooth brain surface, lack of layer specificity bc the neurons derail from radial glia at the wrong times ***step 2 (migration)
- doublecortin (DCX) = helps migration towards cortical plate by regulating the microtubular cytoskeleton; mutation = double cortex syndrome *** step 2 (migration)
- Dab1, Vldlr, Apoer2 = termination of migration and getting off radial glia ***step 3 (stopping)
While cellular division occurs (M phase, mitosis), the nucleus is located _______.
14. Define and describe 3 stages of neuronal migration in the cerebral cortex.
- onset of migration = post-mitotic cell leaves the ventricular zone by riding the radial glia (FLNA mutation --> PH)
- ongoing migration = ride the radial glia to approp. destination (LIS1, DCX mutations --> don't make it to cortical plane)
- migration stop = terminate migration and get off radial glia (Reeler, Dab1, Vldlr, Apoer2 mutations--> layering/patterning problems)
23. Describe neural crest cells and the neuronal populations they give rise to.
- arise from boundary btw the neuroectoderm and the epidermis
- give rise to the PNS, pigment cells, and cartilage
What region of the cerebellum develops postnatally?
the external granule layer
5. Describe what is known about neurogenesis in the adult brain and discuss key questions for future research.
- Neurogenesis occurs in the adult brain in the dentate gyrus and the subventricular zone of the hippocampus and olfactory bulb
- Cell death also occurs
- Total neuron # remains about constant
What is a secondary zone of neurogenesis?
a hot spot of postnatal neurogenesis
When the plane of cleavage is perpendicular to the ventricular surface, both daughter cells ______ to the ventricular surface and the cells remain in the cell cycle.
When the plane of cleavage is ______ to the ventricular surface, both daughter cells remain attached to the ventricular surface and the cells remain in the cell cycle.
As postmitotic cells accumulate within the preplate (PP), the PP divides into the ______, ______, _____, and _____.
marginal zone (MZ), cortical plate (CP), subplate (SP), and the deep ventricular zone
What secretes reelin?
When the plane of cleavage is ______ to the ventricular surface, one of the daughter cells remains attached but the other does not. This is called asymmetrical division.
What happens in the mouse mutant, reeler?
the normal inside-out pattern of cortical organization is inverted
While DNA is being synthesized (S phase), the nucleus is located _____.
As each precursor progresses through the cell cycle, the position of the _____ changes.
A daughter cell can detach its processes from the ventricular surface and will ______.
cease dividing (aka post-mitotic)
10. Describe normal postnatal changes in brain morphology and how Autism Spectrum Disorder (ASD) and Down syndrome affect these normal developmental changes in neuronal morphology.
- normal = low neural connection density but interconnections change and increase rapidly during 1st prenatal year; dendrite spines also thicken
- ASD = abnormally high increases in brain size, esp of white matter areas, with smaller neuronal cell bodies and less branching
- Down syndrome = dendritic spines are abnormally thin and short
21. Draw and describe an asymmetric cell division.
When the plane of cleavage is parallel to the ventricular surface, one of the daughter cells remains attached but the other does not. The unattached begins differentiating and migrating.
What is fund within the intermediate zone (IZ)?
neuronal and radial glial processes
When the plane of cleavage is parallel to the ventricular surface, one of the daughter cells remains attached but the other does not. This is called _______.
8. Discuss when and where neurogenesis occurs.
- Most = prior to birth
- exceptions = cerebellum, olfactory system, hippocampus
17. Define preplate and subplate with respect to neuronal migration.
- preplate = 1st stage of corticogenesis btw pia and ventricular zone; contains the first-born "pioneer" cells (lots of Cajal-Retzius cells)
- subplate = below the 6 cortical layers
What are the 3 distinct stages in neuronal migration?
- onset of migration
- ongoing migration
- migration stop
9. Describe two ways in which function of GABA receptors is developmentally regulated.
- Many GABA receptors and subtypes present in developing brain
- function changes as eq potential for Cl- changes
- Cl- is elevated during development to have more depolarized value
- ECl activation leads to depolarization and excitation --> increased sz susceptibility in neonates
The nervous system begins as a flat epithelium known as the _____.
Neurons migrate into the _____ using radial glia as a scaffold.
2. Describe what is meant by a neuron's birthdate and discuss whether a neuron's birthdate influences its differentiation.
birthdate = last round of DNA synthesis (S phase); earlier-born neurons are located more medially than their later-born counterparts, which have to travel farther and become more lateral/superficial layers (EXCEPT in the retina)
Cells in each of the 3 secondary zones of neurogenesis all have what 3 characteristics in common?
- arise in a ventricular zone
- migrate before exiting the mitotic cycle
- proliferate postnatally in non-ventricular zone locations
16. Describe when cell death occurs in the nervous system.
About half of original cell population dies due to pattern recognition, brain morphogenesis, and removal of unnecessary neurons and matching populations to targets
During the 2 gap phases (G1 and G2), where is the nucleus located?
intermediate within the cell
Once a cell leaves the mitotic cycle, it _____.
also leaves the ventricular zone