Exam 1: Lecture 3 Flashcards
____ is acquisition of glial-class identity
gliogenesis
some radial glia progenitors give rise to glia after neurogenesis
shh controls pattern of specification in neural progenitors. This sets up ___ ___
progenitor domains
Motor neurons from __ domain
Olig2
Spinal interneurons derive from ___ and ____ domains
Nkx2.2
Pax6-Irx3
Do motor neurons differentiate at higher/lower rate than interneurons
higher rate
___ induces expression of Olig2, which directly promotes neuronal differentiation in motor neuron progenitors by suppressing the expression of HES GENES (negative regulators of neuronal differentiation)
Shh
Genetic program that defines the identity of corticospinal neurons will have
instruction for brain region, structure, class of neuron, subtype
Broad specification of progenitor domains by
extracellular morphogens
Different progenitor domains give rise to different
classes of neurons
FGF- __ neuron
BMP2,4 ___ neuron
CNS neuron
PNS neuron
Waddington’s binary decisions
bifurcates into different grooves goes the marble
What is the problem with canalization? Can we change landscape?
Pluripotent reprogramming
Direct conversion
YES!
Why is reprogramming neurons cool?
make specific types for drug test and disease model
patient derived neurons
replacement therapy
Directed differentiation into a specific type of neuron/glial cell:
Genetic programs encoding neuron/glia ______
subtype identity
need to know this to make desired cell
When Caudal signals (RA/some wnts) are gone…
Go rostral
If ventralizing signals blocked
dorsal telencephalic progenitors induced
EXCITATORY = dorsal
Add ventraling signals
INTERNEURONS = ventral (GABA)
Specific combinations of _____________ _______ can be added to further specify neuron identity (DA< SE, Cholinergic)
transcription factors
What factors bring somatic cell back to pluripotent state?
Yamanaka factors
Advantages of iPSCs
limitless source of neurons
used as patient specific therapy -lower risk of rejection
reduce ethical issues
Cons of iPSCs
pluripotent origin- risk of tumor formation
Pros of directly reprogrammed cells
reduced tumorigenic potential
patient-specific lower risk of graft rejection
reduced ethical issues
Cons of directly reprogrammed cells
finite number of neurons can be produced protocols efficiency remains low
Disk model:
no hierarchy
pluripotent state just one of possible states
can be bypassed
extrinsic factors tilt the disk and transcription factors guide
Can pericytes from adult human brain (biopsy) reprogram into neurons?
Yes
The process by which neurons send out axons to reach their targets
Axon navigation
The process by which axons select their target structure and specific target neurons
Target selection
The process by which synaptic targets are recognized by growing axons, and initial contact and communication between neurons is established.
Usually connections exuberant during early development
Synapse formation
The process by which synaptic connections refined.
Unnecessary connections eliminated and function circuits strengthen
Circuit maturation and entrainment
Growth cone:
___-zone: actin-rich lamellipodia and filopodia
___-zone: microtubule more stable
P zone
C zone
Main molecular sign posts for growth cone?
1) Guide post cells
2) Long-range cues (attractants/repellants)
3) short-range cues (adhesion or repulsion)
cells important decision points in axon’s route
Guidepost cells
Navigate a much simpler environment as tissue is less developed
They served as trail blazers or scaffold for
other axons that navigate the pathway after them.
What are they?
Pioneer axons
Short range REPULSION
actin depolymerization
Short range ATTRACTION
microtubule stabilization
short range cues provide ___ for axon growth
substrates
different types of neurons shows preference for a particular ECM protein depending on _____
ECM proteins promote ____ ___
Receptors
axon growth
CAMS signals
1) Guidepost cells
2) axon _____
fasciculation
Attractant or repulsion:
NGF
attractant
Attract/repulse:
Netrin/Ephrin/Wnt
both
Semaphorin/slit
repellant
How can some attract and repulse
cAMP levels and receptor type
The order of signals in sequence influences navigation.
What is this called?
spatiotemporal regulation
Desensitization to signals by ___ of receptors or other interactions
degradation
Commisural axons (crossing signals)
Robo receptors
Slit
High level ROBO3A
How does crossing work
ROBO3A inhibits ROBO1 so cross to get to DCC
After crossing
Robo1 is like: you ain’t going back
And Robo3B is like: yas girl
And slit is on this team too
Can growth cone do stuff independent of soma?
Yep
How does cell solve length of axon problem, cause the stuff gotta get there?
mRNA transported and stored at tip of axons/dendrites waiting for translation when is needed to meet immediate demand
in growth cone, we got local ___ local ___ and local ___
local translation
local mRNA splicing
local regulation of cAMP/cGMP levels
Do axons growth slower or faster when fasciculate together
faster
What is the defasciculating signal in motor neurons?
beat-1a
Branches usually formed when the leading GC
pauses
Growth factors usually make axons
branch and grow toward target area
The autonomous mechanisms in GC make possible to interpret different signals by GC in
same axon
Matching gradients of expression of ligands in target area, and ligand receptors in axons, established what
topographic map
Activity dependent
mechanisms in final targeting step reflect
cell specific targeting
When growth cone at location
1) filopodia retract
2) GC pre and post membrane tightly apposed
3) vesicles add membrane to immature synapse
4) vesicles release progressively recruits receptors and proteins to postsynaptic density
Connections keep and refined by
activity dependent mechanisms
monocular neurons
layer 4
