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

Abstract

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.

Keywords

• Cajal-Retzius cells
• Bax
• death
• distribution
• postnatal cerebral cortex
• transient neurons
• immature circuits