Cell Lineage of Neurons and Glia Flashcards
(33 cards)
In what region is found the progenitor cells with the ability of becoming neural precursors? How is this specific region called? Via which model organism was the region identified?
Genetic screens in the Drosophila allowed to identify the proneural region, which is part of the ventral ectoderm.
How can be identified potential neuroblasts?
They express proneural genes (achaete-scute TFs).
The proneural region contains clusters of potential neuroblasts. Usually, only one potential neuroblast per cluster actually becomes a neuroblast. Which mechanism is at the root of this process? What experiment demonstrated the relevancy of this model?
In a cluster, potential neuroblasts mutually inhibit and only one (random) cell can become a neuroblast. Ablating one neuroblast leads to its replacement by another neuroblast, suggesting that potential neuroblasts generates surround inhibition.
What signaling system would underlie the surround inhibition mechanism of potential neuroblasts?
Delta-Notch signaling.
What is happening if either Delta or Notch are KO?
Overproduction of neuroblasts and underproduction of epidermal cells.
Is Delta-Notch a cell-to-cell interaction signal or is it a secreted signal?
Cell-to-cell interaction signal.
Delta is the _____, whereas Notch is the _____.
Delta is the ligand, whereas Notch is the receptor.
What is happening downstream of Notch?
Notch activation via Delta binding ->protease activation ->intracell. domain of Notch cleaved -> enters nucleus and interacts with TFs that block proneural transcription.
What is determining which cell becomes the neuroblast in a cluster of potential neuroblasts?
The cell that happens to have the highest Delta expression (random).
Explain in detail the surround inhibition mechanism of Delta-Notch signaling.
The cell with higher Delta expression causes the Notch signaling of its neighbouring cell to increase. The increasing Notch signal inhibits the expression of achaete-scute proteins. Downregulation of achaete-scute proteins decreases expression of Delta. Decrease in delta expression causes the initial neighbouring cell to have lower Notch signaling, which allows more Delta to be expressed (and the cycle repeats). Less Notch signaling = neural fate.
What could be one TF that is downregulated by Notch signaling?
BHLH.
Which signal can control Notch activity? In what documented process is it involved?
Numb. Involved in the differentiation of sensory organ precursors in Drosophila (SOP).
What is the consequence of the asymmetric distribution of Numb in SOPs daughter cells?
Some daughter cells acquire Numb and other don’t. Therefore, some cells can acquire a neural fate (acquire Numb) and the others become epidermal.
True or false: neural fate determination is always random.
False. Yes it is random if determined by Delta-Notch signaling, but can also be pre-determined by acquisition of Numb (inhibiting Notch).
True or false: humans have one more ventricular zone than mice.
True, the outer subventricular zone.
From what progenitors do arise radial glial cells? Provide two essential functions of RGCs.
Originate from neuroepithelial cells in the ventricular zone. They are the progenitors of neurons and glia during development. They also provide a scaffold for neuronal migration into cortical layers.
At different time points during development, radial glial cells divide into different cellular identities. State in what cellular identities they divide 1) early in dev. 2) mid. dev. and 3) end of development.
- Amplification stage: neuroepithelial cells divide symmetrically.
- Middle stages: RGCs divide asymmetrically to give rise to both neurons and RGCs.
- Late stages: RGCs give rise to oligo. and become astrocytes.
Explain how oblique division in RGCs leads to the generation of neurons.
Oblique divisions of RGCs asymmetrically distribute apically localized proteins (Par3) in the two daughter cells. The daughter cells with high Par3 concentration conserves its RGC phenotype because Par3 inhibits Numb, relieving its inhibition on Notch signaling (binding to its intracellular domain). The other daughter cell still has active Numb signaling, therefore acquiring a neural fate.
Neurons and glia of the PNS originate from which progenitor cells.
Neural crest cells.
Which signal imposes neuronal identity for PNS cells? Which signal for Schwann cell identity?
BMP signaling.
Glial growth factor (GGF).
How are PNS cells differentiated in their specific neural or glial identities?
By the environmental cues they encounter while migrating.
In the CNS, from what region are originating the cells migrating to different cortical layers?
The ventricular zone.
The superficial layers of the cortex are most likely composed of old or new neurons/glia?
New (young, later born).
What can be experimentally done to demonstrate that the positioning of cortical neurons is age-dependent?
Injecting the cortex at different time intervals with a dye that stains specific cortical neurons.
