New version page

Bisc 407 Discussion Notes

This preview shows page 1 out of 4 pages.

View Full Document
View Full Document

End of preview. Want to read all 4 pages?

Upload your study docs or become a GradeBuddy member to access this document.

View Full Document
Unformatted text preview:

Bisc 407 Discussion 2/4/21 Lecture 3: Neuronal proliferation relies on symmetric and asymmetric cell division - Huge exponential division in neuronal cells day 14-22 - You need a balance between making enough cells to become organ tissue but also telling them what they become - How do we get the cell number to increase? Different kinds of cell division – mostly symmetric division o Can’t do that forever because peripheral cells need an identity at some point – switch to asymmetric division - Before the 14 days, the embyo decides where’s the anterior, posterior, dorsal and ventral, and what’s going to become neural tissue vs skin - Can a generalized cell go back to an ungeneralized form? Like can glial progenitors revert to neural progenitors? Not naturally. But you can induce pluripotency in lab. Do I become a neuronal progenitor or glial progenitor? Focusing on delta and notch - Imagine two cells with equal amounts of delta and notch. Delta disngaling randomly increases in one cell than the other, which signals to the other cell. This results in decreased delta signaling in the other cell. No delta signaling from the other cell means no notch signaling from the original cell, resulting in enhanced delta signaling in the original cell. You’re keeping more and more delta in one cell and more and more notch in the other. - Higher delta = neuron percursor. Higher notch = becomes glial precursor - Glia experience high notch. Within the same cell, if there’s a lot of delta, there’s gonna be less notch - inverse relationship and competition. All happens due to a random imbalance. - You can fine tune the signaling and control what KIND of glia it becomes – astrocyte vs oligodendrocyte (with a little bit of notch inhibitor) Why does the asymmetric division matter – how our cortical cells get where they need to be - Radial glia grows out like a scaffold and neurons “climb” up - Radial migration = center (cortex) of brain out to the skull - Neuron needs guidance to carry its heavy ass WAP ass nucleus up - Focus on ventricular zone of the layers = where all of mitosis and cell division occurs and where new neurons are being made - Inside neurons are the old ones. Newest ones on the outside. New neurons are jumping past the old ones (leapfrogging) - Reelin mutants cause detachment issues – causes inverted layering because the neurons have a hard time detaching from the radial glial cell. Doesn’t jump off until it absolutely has to – at the skull- Lissencephaly – migration issue. Issue in protein called doublecortin. Not a layering issue. Doublecortin is associated with microtubules, which are very strong. Need this strength to move heavy neuron nucleus up the radial glia. This machinery needs to move up and drag the nucleus up the cell (nuclear translocation). Kind of like axon guidance but axon guidance relies on actin instead. With this disease you don’t get this proper movement. - Tangential migration is movement perpendicularly through the radial glia. Insread of using this as a scaffold, neurons use pre-laid-out axons to move. - Free migration is what you see with neural crest cells. BMP turns on transcription factors that express proteases, enabling the cells to embark on their journey to the periphery. Proteases kinda cut through the dense ECM Lecture 4: Neurotransmitter Identity and Neuronal Survival - Neural crest cells differentiate into sympathetic and sensory neurons. Transcription factors and their receptors define which one the neuron becomes. - With no extra signaling, sympathetic neurons will becomes noradrenergic. With signaling, it becomes cholinergic. Cholinergic fate is determined by target-generated cytokines. - Default state is for sympathetic neuron to become noradrenergic - CNS is hardwired in early development. You don’t see these transcription factors in mature neurons. Key points: neurotransmitter fate in CNS is defined bvery early on, before any migration, differentiation and cell fates. They neurotransmitter identity was already hardwired. - Signaling from muscle targets is needed to promote motor neuron survival - In control embryo, 50% neuron survival (normal). With removed limb, only 10% survive. Target provides pro-survival signal. Adding extra target tissue (limb bud) results in 75% neuron survival. Control still only keeps 50%. Having more of the target present, it’s possible that the target is providing survival. - Treat with curare, 75% of neurons survive  blocking muscle activity with this drug rescues neuron that would normally die. Why?? - Our system makes way too many neurons. These neurons have to approach a target like a muscle. This muscle releases neurotropic factor globally so all the neurons experience it. Synaptic activity drives local release – some neurons get way more than the neighboring neurons. The one or two neurons that initiated the activity with the muscle get the most neurotrophins, which are pro-survival signals for neurons. The other neurons end up dying (apoptosis). This is how we insure stable synapse formation.Key things: understand global vs local release and what causes the switch. Remember that neurotropins are needed to provide the survival signals to neurons. - There are two types of death signals – extrinsic vs intrinsic (mediated by the mitochondria). Some neurons only survive for weeks and that’s preprogrammed - Extrinsic implies that there’s a cue that’s promoting the death from out of the cell - Both pathways converge onto one protein and that results in cell death (caspase 3) What about way to promote survival? - NGF and trkA. TrkA dimerizes as NGF binds and that induces a survival pathway by inhibiting caspase 9. Neurotropins inhibit caspases and therefore cell death. High and sufficient levels of neurotrophins activates pro-survival pathways and inhibit pro-death pathways. This stuff is def on the exam. Lecture 5: Cell Polarity and Axon Guidance - There have to be ways to define the polarity (one end having axon and the other having dendrites) - Neuron grows out neurites, from which only one becomes an axon and the rest become dendrites – implies that the axon is suppressing every other neurite’s ability to become an axon. Cut the axon  suppression factor is gone and another neurite is able to become an axon instead of a dendrite. - SAD kinase  necessary for proper neuron polarization. If you


View Full Document
Loading Unlocking...
Login

Join to view Bisc 407 Discussion Notes and access 3M+ class-specific study document.

or
We will never post anything without your permission.
Don't have an account?
Sign Up

Join to view Bisc 407 Discussion Notes and access 3M+ class-specific study document.

or

By creating an account you agree to our Privacy Policy and Terms Of Use

Already a member?