Transcription factors make a turn into migration

Abstract

The formation of the brain depends on a tightly regulated process of proliferation, neuronal fate specification and migration which eventually leads to the final architecture of the cerebral cortex. The specification of different neuronal subtypes depends on a complex developmental program mastered by several transcription factors. Besides, it was shown that the same transcription factors can subsequently control neural migration. However, the mechanisms of this regulation are still unclear. Two papers recently published by Heng et al. and Nóbrega-Pereira et al. confirm that these transcription factors are involved in controlling neural migration. In addition, these studies show that these transcription factors can control neural migration via different molecular mechanisms: Heng and coworkers show that Neurogenin 2 controls neural migration by directly regulating the expression of the small GTPase Rnd2 (a modulator of cytoskeletal dynamics); whereas Nóbrega-Pereira and colleagues demonstrate that Nkx2-1 establishes the response to guidance cues, in migrating interneurons, by directly regulating the expression of the semaphorin receptor Neuropilin 2.

Taken together, these findings support the idea that transcription factors are reused during development to control neural migration and they shed light on the molecular mechanisms underlying this regulation.

Figure 1

(A) Schema of a coronal section of an E13,5 mouse brain highlighting the major migratory routes of cortical neurons. Pyramidal neurons originate in the ventricle wall and migrate outward to the upper cortical layers. Striatal and cortical interneurons are born in the MGE. Next, striatal interneurons enter directly the striatum; conversely, cortical interneurons are repelled by the Semaphori3A/3F expressed by the striatum and take their way to the cortex. (B) In pyramidal neurons, Neurog2 enhances the expression of Rnd2 which, in turn, regulates cell motility by impinging on cytoskeletal dynamics and, possibly, on Plexin signalling at different levels. (C) Striatal interneurons are insensitive to Semaphorins induced repulsion because Nkx2-1 represses the expression the Semaphorin receptor Neuropilin2; therefore, these interneurons are sorted to the striatum.