Enhanced Abventricular Proliferation Compensates Cell Death in the Embryonic Cerebral Cortex.
Loss of neurons in the neocortex is generally thought to result in a final reduction of cerebral volume. Yet, little is known on how the developing cerebral cortex copes with death of early-born neurons. Here, we tackled this issue by taking advantage of a transgenic mouse model in which, from early embryonic stages to mid-corticogenesis, abundant apoptosis is induced in the postmitotic compartment. Unexpectedly, the thickness of the mutant cortical plate at E18.5 was normal, due to an overproduction of upper layer neurons at E14.5. We developed and simulated a mathematical model to investigate theoretically the recovering capacity of the system and found that a minor increase in the probability of proliferative divisions of intermediate progenitors (IPs) is a powerful compensation lever. We confirmed experimentally that mutant mice showed an enhanced number of abventricular progenitors including basal radial glia-like cells and IPs. The latter displayed increased proliferation rate, sustained Pax6 expression and shorter cell cycle duration. Altogether, these results demonstrate the remarkable plasticity of neocortical progenitors to adapt to major embryonic insults via the modulation of abventricular divisions thereby ensuring the production of an appropriate number of neurons.
Institut Jacques Monod, CNRS UMR 7592, Université Paris Diderot, Sorbonne Paris Cité, 15 Rue Hélène Brion , 75205Paris Cedex, France.
Betty
B
Freret-Hodara
Institut Jacques Monod, CNRS UMR 7592, Université Paris Diderot, Sorbonne Paris Cité, 15 Rue Hélène Brion, 75205 Paris Cedex, France.|Center for Interdisciplinary Research in Biology (CIRB)-Collège de France and INRIA Paris, EPI MYCENAE, 11, Place Marcelin Berthelot, 75005 Paris, France.|Ecole Doctorale Cerveau Cognition Comportement (ED3C, ED n°158), Université Pierre et Marie Curie, 7 Quai Saint Bernard, 75005 Paris, France.
Yi
Y
Cui
Institut Jacques Monod, CNRS UMR 7592, Université Paris Diderot, Sorbonne Paris Cité, 15 Rue Hélène Brion , 75205Paris Cedex, France.
Amélie
A
Griveau
Institut Jacques Monod, CNRS UMR 7592, Université Paris Diderot, Sorbonne Paris Cité, 15 Rue Hélène Brion , 75205Paris Cedex, France.
Lisa
L
Vigier
Institut Jacques Monod, CNRS UMR 7592, Université Paris Diderot, Sorbonne Paris Cité, 15 Rue Hélène Brion , 75205Paris Cedex, France.
Yoko
Y
Arai
Center for Interdisciplinary Research in Biology (CIRB)-Collège de France and INRIA Paris, EPI MYCENAE, 11, Place Marcelin Berthelot , 75005Paris, France.
Jonathan
J
Touboul
Institut Jacques Monod, CNRS UMR 7592, Université Paris Diderot, Sorbonne Paris Cité, 15 Rue Hélène Brion , 75205Paris Cedex, France.
Alessandra
A
Pierani
D000818:Animals; D016923:Cell Death; D049109:Cell Proliferation / Q000502:physiology*; D002540:Cerebral Cortex / Q000166:cytology* / Q000196:embryology*; D018507:Gene Expression Regulation, Developmental / Q000502:physiology; D008822:Mice, Transgenic; D058953:Neural Stem Cells / Q000166:cytology; D055495:Neurogenesis / Q000502:physiology; D009474:Neurons / Q000166:cytology*
abventricular proliferation; cell death; compensation; embryonic cerebral cortex; upper layer neurons