Exam 1: Lecture 2 Flashcards
neural progenitor expansion and neurogenesis occurs in
ventricular zone
After mitosis daughter cells become ___ post mitotic
fixed
During neuroepithelial cell division, ____ allows cells to divide unrestricted while maintaining dense packing
interkinetic nuclear migration
Neuroepithelial (NE) cells:
Division type
progeny
Symmetric
2x NE
Radial Glial progenitors (RG):
division type
progeny
Asymmetric
neurons, BPs
Basal Progenitors (BP):
division type
progeny
symmetric
two neurons
The length of cell cycle increases during embryogenesis mainly due to lengthening of ___ phase.
G1
reflects regulation of S entry
longer G1= increased chance of making neuron
Symmetric Division
neuroepithelial/radial glia
VERTICAL CLEAVAGE bigger neuroepithelium (horizontal)
tangential expansion
if cleavage plane horizontal or tilted
asymmetric division
____ proteins control cleavage plane
SNARE
Symmetric division needs ___ interactions of SNARE, asymmetric needs ____
heterophilic (basolateral apical)
homophilic (basolateral x2 )
What if apical t-SNARE not present?
only 1 daughter cell is neuron
What is the molecular marker selectively expressed in essentially all neuroepithelial cells about to undergo neurogenic division?
Tis21
Humans have more (basal/apical) progenitors
basal
more diverse
Symmetric division (NP SELF-RENEWAL) increases \_\_\_\_ progenitors
radial glia
Asymmetric (NEUROGENIC DIVSION)
produces
radial glia
column of neurons destined to all layer
Symmetric division of INTERMEDIATE progenitors in SVZ produce
Radial glia
produce multiple columns of neurons (or radial column) destined to all layers of cortex
Size of ___ (with INTERMEDIATE PROGENITORS) predicts the location of gyra and sulci in human cortex.
SVZ
Radial unit hypothesis
cortex develops as array of interacting cortical columns or radial units, each of which originates from progenitor in VZ
Protomap
primordial identity of each function cortex area is encoded with cortical progenitors prior to formation of cortical layers.
Mutations in genes regulating interkinetic nuclear migration (INM) produce
deficits in NP proliferation (microcephaly)
NP proliferation is regulated by the length of the ___ ___
cell cycle
mutations in genes that regulate ______ (Pax6/filamin) OR _____ (Rac1, cyclin D2, Numb stuff) affect NP proliferation and final position of neurons
cell cycle length
cell cycle exit
Longer NP proliferations creates new opportunities for ____
regulation
regulated by factors secreted from afferent connections
Polymicrogyria
regions of complex and excessive number of cortical convolutions with miniature gyri fused and superimposed together
GPR56 16q130 bilateral
Enviornment: intra utero ischemia, prenatal infection, toxoplasmosis, cytomegalovirus
Symptoms: epilspy, delay, cerebral palsy, ID, dyslexia
migrating cells- describe them
elongated soma,
trailing process which will be axon
Excitatory neurons are generated in an ____ fashion
inside-out
____ are generated in non-cortical locations for the most part
interneurons
How do we track location of progenitors at different points in development?
3H-thymidine BrdU during S phase right before division
Can use prospective and retrospective lineage tracing
Genetic recombination lineage tracing
Fate mapping with CRE
Green: Wnt1-CRE: recombination occurs
Red: no cre, no recombination. stop tomato
Sequential competence:
A –> B –> C
things only from certain things
Independent
multipotential lineage vs. unipotential lineages
multi: red vs. blue
‘
uni: red vs. blue then light vs. dark
Nest multpotential lineages
random stuff?
The sequential competence state model states that progenitors potential becomes progressively ____ over time
Restricted
Layers 6 –> 123
but 123 –> 123
Tangential migration:
interneurons migrate like this
brings neurons orginated ___ to structure and gives rise to structures of mixed origin
far away
Do radial and tangential migration occur same time?
Yes
Radial migration relies on
short range and cell adhesion signals
Tangential migration
relies on all types of signals: short range, long range, diffusible, cell-cell interactions
In caudal neural tube ___ migration is more predominant
radial
___ migration = development of cerebellum. External granule cell layer of the cerebellum comes from rhombic lip at the lateral border of the 4th ventricle. This gives rise to all granule cells.
Tangential
In thalamus, what plot twist
outside born first, inside last
inside= correspond to nuclei close to 3rd ventricle
outside= nuclei close to border of thalamus
Migration disorder:
Periventricular hetertopia/filamin1 mutation
neurons don’t migration out of VZ
When ongoing migration fails:
Lissencephaly (LIS1 and DCX)
proper inside out pattern but
imprecise manner
When ongoing migration fails:
Double cortex
mutation in DCX (x linked gene)
Due to x-inactivation, one neuron population with mutation doesn’t migrate correctly and stays below cortical plate
If final stage of migration fails (reeler mouse)
rough inversion of inside out pattern of cortical migration
excess of neurons normally cell-sparse marginal zone.
Dab1 is involved
Cdk5 and p35:
inverted cortical plate, but it’s special
leave marginal zone intact
don’t disrupt accurarcy with which neurons of similar type laminate
____ mutant: subplate in middle of cortical plate
Cdk5
___ mutant: subplate is beneth cortical plate
p35
What is the most common symptom of migration disorder
seizure
