Maintaining Subtype-Specific Neuronal Identity in the Mammalian Cerebral Cortex

Abstract

In the mammalian cerebral cortex, distinct classes of neurons are generated embryonically and maintain their subtype-specific identities throughout the lifetime of the organism. While their developmental programs have begun to be elucidated, much less is known about the mechanisms that preserve their identity through time. We showed previously that Fezf2 is a selector gene for corticospinal motor neurons (CSMNs) and the first selector gene known for any class of projection neurons in the cortex. Here, we hypothesize that Fezf2 is a terminal selector gene and is therefore needed to maintain CSMN identity throughout the life of the animal. We employed a genetic strategy to conditionally delete Fezf2 specifically from CSMNs at distinct postnatal time points, when CSMN fate specification and connectivity have already been established. Our data shows that while Fezf2 is needed early postnatally to maintain the molecular identity of CSMNs, it is not necessary in the adult. By exploiting Fezf2 function in mature CSMNs, our work suggests that other mechanisms are used for neurons to maintain their identity and function in the mature cerebral cortex.