NEUS 609 - Generation, Migration, & Survival of Neural Cells I

proliferative pseudostratified epithelium

lining of ventricular cavity of developing neocortex made of radial glial cells in between a pial and apical (outside & inside respectively) surface.

• where excitatory projection neurons proliferate

G1

at the ___ phase of cell cycle, the nucleus of radial glial cell is near the ventricular surface. The cell extends a process to anchor itself on pial surface.

• growth & prep for DNA synthesis

S stage

at the ___ of cell cycle the nucleus of radial glial cell is near the pial surface

• DNA replication

G2

at the __ phase of cell cycle the nucleus of radial glial cell is back to ventricular surface. The cell retracts the process from pial surface.

• prep for mitosis

Mitosis

__ phase of cell cycle the nucleus of radial glial cell is still near ventricular surface.

• cell division/split

symmetric cell division

the 2 product cells are BOTH progenitors/stem cells because they both inherit apical connections aka transmembrane protein complexes

asymmetrical cell division

the 2 product cells are different

• one stays a stem cell/progenitor

• the other becomes a neuroblast

same process/radial cell migration as for symmetrical cell division, just a different end result.

progenitor cell

• inherit apical connections/transmembrane proteins/Par-complexes

• inherit primary cilium

• inherit mother centrosome

• active Notch signaling

neuroblast

• no apical connections

• no primary cilium

• inherit daughter centrosome

• inherit/express Numb

• Notch signaling inhibited

apical polarity/connections

junctions between ventricular membrane and radial glial cells

• made of transmembrane proteins

• Par-complexes

• asymmetrically inherited

• give stem cell characteristic

primary cilium

it protrudes selectively from apical plasma membrane into the lumen of ventricle aka into the embryonic CSF.

• asymmetrically inherited

• give stem cell characteristic

centrosome

major microtubule organizing center containing 2 centrioles (mother daughter) that duplicate before cell division giving rise to mother & daughter ___

• mother ___ gives stem cell characteristic when inherited

• daughter __ gives neuroblast characteristic when inherited

• anything coming from the “original cell” has a stem cell characteristic

Notch signaling

pathway that inhibits/suppresses pro-neural expression

• receptors on surface of progenitor cells

• ligands expressed by neuroblasts/newborn neurons leading to lateral inhibition (aka making sure the neighbors of neuroblast stays stem cells)

• pathway active in progenitor cells

• extracellular signal

Numb

protein inhibiting Notch pathway when expressed

• intracellular protein

• expressed/inherited only in neuroblast

lateral inhibition

• Numb independent process

• happens during interphase

• notch receptors on surface of progenitor cells binds to ligand expressed by nearby neuroblast

• INHIBIT NEURAL DIFFERENTIATION

6

In the cortical region, there are ___ layers of gray matter on top of white matter base

• 1 closest to the pial surface

• __ closest to the ventricular surface/inside of brain

inside, outside

neurogenesis follows an ___-first ___-last process

BRDU

chemical marking proliferating cells by binding to newly synthesized DNA

• injected in progenitor cells to label birthdate/lineage

• how layers of cortex were discovered

coherent RGP model

all stem cells are the same and layer based on division timing

heterogenous RGP model

some populations of stem cells are predetermined to be neurons in a specific cortical layer

projection excitatory neurons

NEURON TYPE: ___

ORIGIN/LOCATION: dorsal telencephalon ventricular and subventricular zones

GENES EXPRESSED: neurogenin & Ngn 1/2

inhibitory GABAergic neurons

NEURON TYPE: ___

ORIGIN/LOCATION: medial & lateral/caudal ganglionic eminences as well as embryonic preoptic area

GENES EXPRESSED: Gsh 1/2, Nkx2.1, Ascl1

overlapping

generation of neurons, astrocytes, and oligodendrocytes occur in a temporarily distinct yet ___ pattern

• neurons first, glial cells develop later