<i>Foxg1</i> Suppresses Early Cortical Cell Fate

TLDR

During mammalian corticogenesis, progenitor cells progressively restrict the types of neurons they can generate, yet the mechanism that determines early versus late neuron fate remains unknown. The study investigates whether the telencephalic transcription factor Foxg1 suppresses the generation of the earliest‑born Cajal‑Retzius neurons. By conditionally inactivating Foxg1 in cortical progenitors that normally produce deep‑layer neurons, the authors tested Foxg1’s role in suppressing Cajal‑Retzius fate. Foxg1 null mutants exhibit an excess of Cajal‑Retzius neurons, and conditional loss in deep‑layer progenitors confirms that Foxg1 is constitutively required to suppress this fate, showing that competence for early neuron generation is actively suppressed but not lost.

Abstract

During mammalian cerebral corticogenesis, progenitor cells become progressively restricted in the types of neurons they can produce. The molecular mechanism that determines earlier versus later born neuron fate is unknown. We demonstrate here that the generation of the earliest born neurons, the Cajal-Retzius cells, is suppressed by the telencephalic transcription factor Foxg1. In Foxg1 null mutants, we observed an excess of Cajal-Retzius neuron production in the cortex. By conditionally inactivating Foxg1 in cortical progenitors that normally produce deep-layer cortical neurons, we demonstrate that Foxg1 is constitutively required to suppress Cajal-Retzius cell fate. Hence, the competence to generate the earliest born neurons during later cortical development is actively suppressed but not lost.