Neurobiology 3

Nature

Lineage derived cues

Nurture

Environmentally-derived cues

Progenitor cells

Mitotic dividing cells, respond spatially or temporarilly variying cues that determine cell fate

Non-mitotic cells

Can no longer divide

Differentiating cells

Transcription factors from earlier phase induce the expression of transcription factors regulating specific aspects of differetiation (neurotransmitter, etc…)

Ontogeny

Developmental origin

sensory bristle 4 different types

2. Bristle cell

3. Socket shell

4. Sheath cell

SOP (sensory origin precurosor) cell

notch and numb determine which cell turns into what

Where does numb distribute to?

One daughter cell in SOP cell division

If you have no numb signaling..

-you are numb to life and senses because the hair cells won’t develop properly

-elevated socket and bristle cells= prevents neural development

If we get rid of notch

only sheathed and neuronal cells

there are many different transcription factor families that specify cell identity

interacts with other TFs to form hetereo or homo-dimers (by interacting with loops)(knitting) = subspecific cell fates

Mash 1 gone

no pan neuronal genes

Class I factors dominate

(minimal SHH)

Class II factors

(high SHH)(sonic hedgehog)

Interneuron types in spinal cord

all cell types generated through differential expression of transcription factors (don’t need to know types)

spinal cord

each layer has has their own transcription facotrs and gene encoding specific proteins

What genes do these TFs regulate?

gives us ideas whether the cells are excitatory or inhibitory, involved in both, and th phenotypes

Layer 1

intercortical axons and synapses

Layer 2/3

intercortical and callosal projections

L4

Neurons receiving thalamocortical projections

Layer 5/6

Layers of cerebral cortex

Different genes and TF’s in each layer

fezf2

“zinc finger” domains that bind DNA

Organoids

Cortical layers develop in organoids similar to fetal brains

Layer V CSMNs are missing in Fezf2 KO mice

CMSNs have large cell bodies- missing in the KO 

gain of function Fezf2 experiment

see expression in wrong region (l4) causes it to change the layer that it is within

which of the following belongs to the Zinc finger transcription factor family?

Fezf2

What genes does Fezf2 regulate?

RNA seek or microRNA libraries (tagged GFP on fezf2+ cells and then perform microarrays to determine genes-Ephb1 (epherin)

epherins are involved in..

axon guidance

In the absence of Fezf2 or ephb1…

CSMN axons project into the anterior commissure (AC) instead of projecting into the corticospinal tract (CST)

Fezf2 is highly expressed in which of the following layer during the development of the cortical plate?

Layer 5