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Enhanced Abventricular Proliferation Compensates Cell Death in the Embryonic Cerebral Cortex
Betty Freret-Hodara1, Yi Cui2,3,4, Amélie Griveau1
1Institut Jacques Monod, CNRS UMR 7592, Université Paris Diderot, Sorbonne Paris Cité, 15 Rue Hélène Brion , 75205Paris Cedex, France.
Cerebral Cortex (New York, N.Y. : 1991)
|September 14, 2016
Summary
The developing brain compensates for early neuron loss by increasing progenitor cell proliferation, maintaining normal cortical thickness. This highlights the remarkable plasticity of neural stem cells during development.
Area of Science:
- Neuroscience
- Developmental Biology
- Computational Biology
Background:
- Neocortical neuron loss is presumed to reduce brain volume.
- The developing brain's response to early-born neuron death remains poorly understood.
Purpose of the Study:
- Investigate how the developing neocortex compensates for significant early neuron loss.
- Identify the cellular and molecular mechanisms underlying this compensatory response.
Main Methods:
- Utilized a transgenic mouse model with induced apoptosis in early postmitotic neurons.
- Developed and simulated a mathematical model of cortical development.
- Experimentally validated model predictions in mutant mice.
Main Results:
- Despite massive early neuron apoptosis, cortical plate thickness was normal at E18.5.
- Overproduction of upper layer neurons occurred at E14.5 in mutants.
- A mathematical model identified increased intermediate progenitor (IP) proliferation as a key compensation mechanism.
- Mutant mice exhibited increased abventricular progenitors, including basal radial glia-like cells and IPs.
- IPs showed enhanced proliferation, sustained Pax6 expression, and shorter cell cycles.
Conclusions:
- Neocortical progenitors display significant plasticity to counteract embryonic insults.
- Modulation of abventricular divisions by progenitors ensures appropriate neuron production.
- The developing brain can adapt to substantial cell death through progenitor proliferation adjustments.

