L1 Stem Cell Niches & Developing Brain Flashcards
Neural cell fates are determined in a __ manner
spatio-temporal
Neural stem cells are __potent
multi
Glial progenitors are __potent
bi (give rise to astrocytes & oligodendrocytes)
Neural progenitor cells can be either…
neurogenic or gliogenic
The neural plate is generated from __ by neural induction
dorsal ectoderm
__ antagonists induce generation of neuroectoderm
BMP antagonists (repress epidermal fate-inducing BMPs in overlying dorsal ectoderm)
Neural plate folds into __ , which detaches from epidermis
neural tube
Which occurs first: neurogenesis or gliogenesis?
Neurogenesis
The two types of division that NPCs of neural tube undergo
Symmetric division and asymmetric division
Symmetric division vs asymmetric division
Symmetric: two identical daughter cells (stem cells)
Asymmetric: one daughter cell continues dividing, one post-mitotic daughter cell delaminates from epithelium & differentiates into a neuron
What is the purpose of symmetric division?
to increase the number of NPCs to make the required number of neurons for optimal brain development
An example of an insult in early pregnancy that can affect neurogenesis
Zika virus can cause microcephaly
What are Delta and Notch?
Neurogenic genes that inhibit Neurogenin gene expression
What are Neurogenins?
a family of proneural genes that specify neuronal differentiation
What is an important gene for terminal neuronal differentiation?
NeuroD
What is the effect of Delta/Notch signalling?
It inhibits Neurogenin gene expression via TF inhibition
How do stem cells know to stay stem cells?
Lateral inhibition
What is lateral inhibition?
- Discrete groups of neuroectodermal cells begin to express proneural genes & form proneural clusters
- These cells then undergo an inhibitory cell-cell interaction, mediated via neurogenic genes, to determine which cells will differentiate into neurons
- The first cell in proneural cluster begins to differentiate towards a neural fate, and sends out inhibitory signals to its neighbouring cell that inhibits it from becoming a neuron (remain precursor)
Most proneural genes encode…
basic helix-loop-helix (bHLH) transcription factors
Loss of proneural gene function leads to…
decreased neuronal production
Misexpression of proneural genes leads to…
increased neurons in neural tube & conversion of epidermal cells into neurons
Loss of neurogenic gene function causes…
a massive increase in neurons at the expense of other cells (epidermal cells in invertebrates; neural cells in vertebrates)
__ is recruited to apical pole to form the apical complex (Par/Insc/Pins), which directs…
Par complex
directs mitotic spindle orientation
During asymmetric cell division, the parent cell receives the __ complex
apical
Proteins in the apical complex activate Delta/Notch signalling in neuroblasts, which leads to…
- repression of proneural genes (and therefore, decreased neuronal production)
- maintenance of stem cell state
Apical complex causes movement of…
the basal complex (Ccnd2, Trim32) to basal pole
During asymmetric cell division, the daughter cell receives the __ complex
basal
What do basal complex transcription factors do?
- Turn on genes for neural differentiation
- Switch off genes for proliferation
- Inhibit Notch signalling pathway (which de-represses proneural genes)
RGC marker (asymmetric RGC divisions)
BLBP (brain lipid binding protein)
Neural progenitor cell marker (symmetric cell divison)
Nestin (early neural tube)
Does cell division happen at the apical or basal surface?
apical
__ signalling keeps stem cells as stem cells
Delta/Notch
Both daughter cells in symmetric division inherit the __ complex
apical
Which daughter cell inherits the apical complex in asymmetric division?
the one closest to the apical surface
In early development, NPCs are __ positive and __ negative
Nestin positive and BLBP negative
What is neural patterning?
The biological process by which cells in the developing nervous system acquire distinct identities according to their specific spatial positions
What is a major determinant of neuronal cell fate in the spinal cord?
dorsal-ventral positioning
2 signalling centres at the ventral and dorsal midline
- dorsal roof plate
- ventral floor plate
What does the dorsal roof plate secrete?
BMPs (bone morphogenetic proteins)
What does the ventral floor plate secrete?
Sonic hedgehog (Shh)
The absolute concentration of the __ acting on any one cell determines developmental fate
morphogen (e.g. BMP, Shh)
Shh V-D gradient partitions the ventral floor plate into __ discrete progenitor domains, which generate __ different classes of neurons
5 domains, 6 neurons
Does ventral patterning play a role in motor or sensory spinal circuitry?
motor
Does dorsal patterning play a role in motor or sensory spinal circuitry?
sensory
Motor neuron progenitors express…
Nkx6.1 and Olig2
Neuron progenitors in other ventral domains become __
interneurons
V3 interneuron progenitors express __ but not __ and __
express Nkx2.2 but not Pax6 & Olig2
Nkx6.1 turns on expression of __
Olig2 (bHLH TF)
Role of Olig2
induces motor neuron differentiation by activating expression of Hb9 and ISL-1/2
The dorsal alar plate is subdivided into __ major progenitor regions. Describe
2
- most dorsal region (3 progenitor domains): Class A dI1-dI3 interneurons
- intermediate region (6 progenitor domains): Class B dI4-dI6 interneurons
Wnt ligands bind to…
Frizzled receptors and co-receptors LRP5/6
Mature BMP dimers exert their effects by binding to __, leading to…
BMPRs, leading to recruitment and phosphorylation of receptor-regulated Smad proteins (Smad-1/5), which then complex with Smad-4 and translocate to nucleus
Neuron differentiation of Class __ interneurons is BMP/Wnt signalling-dependent
A
The patterning of dorsal spinal cord interneurons requires __ signalling
BMP-Smad signalling
BMP/Wnt signalling turns on expression of __, which are cell type specific determinants of Class A progenitors
Olig3, Atoh1 (dI1), Neurog-1/2 (dI2), Ascl1(dI3)
__ is expressed by all Class A progenitors
Olig3
Olig3 represses __ to specify dI1-dI3
Lbx1
Neurogenesis has mainly been studied in the __, whereas neural patterning has mainly been studied in the __
cortex
spinal cord
