Stem Cells & the Developing Brain Flashcards
WHY is stem cell proliferation is essential during development?
→ to understand how neural cell fates are determined
2 key factors to consider in stem cell proliferation
Molecular factors = genes and transcription factors
Cellular factors = position and timing of cell birth
neural cell fates are determined in…
a spatio-temporal manner (i.e., space & time - where and when a cell is born has a large influence on what it becomes)
What is cell fate regulated by?
a number of factors - but ultimately depends on the integration of intrinsic signals which are genetically inherited from precursor cells and extrinsic signals that come from the environment
Neural stem cell potential?
Multipotent - many potentials!
→ can become a neuron, astrocyte and oligodendrocytes
Glial progenitor cell potetnial?
Bipotent - only gives rise to glia (there are only two types! Astrocytes & Oligodendrocytes)
Where does the nervous system derive from
the ectoderm layer
Bone Morphogenetic Proteins?
a key group of developmental signals
Why would we antagonise BMPs?
to induce differentiation of the neural ectoderm, i.e., the blue print of the nervous system
Importance of Neurogenic Vs Gliogenic signals?
to determine whether neural stem cells choose a neuronal or glial fate
Which comes first in development - Neurogenesis or Gliogenesis?
Neurogenesis precedes gliogenesis in development of the NS
Lateral inhibition?
inhibition of the cell lateral to another cell…
NB in the initial stages of development of the NS
What is key to the behavior of neural progenitor cells?
the Neural tube under goes two types of division
- Symmetric division: - two identical daughter cells
- Asymmetric division: - two daughter cells, however only one continues dividing and the other migrates and differentiates into a neuron
Symmetric Division
NB to increase the pool of neural progenitor cells in order to make the required amount of neurons that are needed by birth
Asymmetrical divison
to maintain a stem cell, but also to give rise to a stem cell which will produce neurons
What marks the onset of neurogenesis?
the switch from symmetric division to asymmetric division
What is the Delta/Notch signaling pathway?
Neurogenic genes which inhibit neurogenin gene expression
What are Neurogenins?
a family of proneural genes which drive neuronal differentiation
When neurogenin expression is blocked..
When neurogenin expression is blocked in both cells to an equal extent, they have equal levels of delta and these stem cells will not differentiate and will maintain a stem cell fate (to increase the progenitor cell pool)
What if one cell increases the expression of the delta ligand?
This will result in a greater signaling through the notch receptro in the blockade of neurogenin in the other stem cell, so this means it will maintain a stem cell fate - the cell with a greater expression of delta: switches on expression of other genes required for neuronal diffrentiation
why can’t cells diffretniate at the same time to become a neuron?
Lateral inhibition - involves delta notch inhibition of neurogenesis which is NB in neuronal differentiation.
- When this process is unbalanced, one of them will undergo neuronal differentiation (asymmetrical)
Most proneural genes encode..
basic helix-look-helix transcription factors
→ loss of proneural gene expression = decreased neuronal production etc
Why is cell division so important in the neural tube?
for populating the developing nervous system with enough cells to ultimately generate the required number for what is needed for normal development
asymmetric division is NB because..
not only does it allow the development of neurons, it also allows us to keep the progenitor cell pool intact
