Targeted Inactivation of Bax Reveals a Subtype-Specific Mechanism of Cajal-Retzius Neuron Death in the Postnatal Cerebral Cortex

Publication date: 20 December 2016
Source:Cell Reports, Volume 17, Issue 12
Author(s): Fanny Ledonne, David Orduz, Judith Mercier, Lisa Vigier, Elisabeth A. Grove, Fadel Tissir, Maria Cecilia Angulo, Alessandra Pierani, Eva Coppola
Cajal-Retzius cells (CRs), the first-born neurons in the developing cerebral cortex, coordinate crucial steps in the construction of functional circuits. CRs are thought to be transient, as they disappear during early postnatal life in both mice and humans, where their abnormal persistence is associated with pathological conditions. Embryonic CRs comprise at least three molecularly and functionally distinct subtypes: septum, ventral pallium/pallial-subpallial boundary (PSB), and hem. However, whether subtype-specific features exist postnatally and through which mechanisms they disappear remain unknown. We report that CR subtypes display unique distributions and dynamics of death in the postnatal mouse cortex. Surprisingly, although all CR subtypes undergo cell death, septum, but not hem, CRs die in a Bax-dependent manner. Bax-inactivated rescued septum-CRs maintain immature electrophysiological properties. These results underlie the existence of an exquisitely refined control of developmental cell death and provide a model to test the effect of maintaining immature circuits in the adult neocortex.

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Teaser

Ledonne et al. report that Cajal-Retzius neuron subtypes display unique distributions and dynamics of death in the postnatal mouse cortex. Conditional inactivation of the pro-apoptotic factor Bax reveals that different pathways control subtype death. CRs that are prevented from dying maintain immature electrophysiological properties in an adult environment.


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