Proneural genes in neocortical development

Abstract

Neurons, astrocytes and oligodendrocytes arise from CNS progenitor cells at defined times and locations during development, with transcription factors serving as key determinants of these different neural cell fates. An emerging theme is that the transcription factors that specify CNS cell fates function in a context-dependent manner, regulated by post-translational modifications and epigenetic alterations that partition the genome (and hence target genes) into active or silent domains. Here we profile the critical roles of the proneural genes, which encode basic-helix-loop-helix (bHLH) transcription factors, in specifying neural cell identities in the developing neocortex. In particular, we focus on the proneural genes Neurogenin 1 (Neurog1), Neurog2 and Achaete scute-like 1 (Ascl1), which are each expressed in a distinct fashion in the progenitor cell pools that give rise to all of the neuronal and glial cell types of the mature neocortex. Notably, while the basic functions of these proneural genes have been elucidated, it is becoming increasingly evident that tight regulatory controls dictate when, where and how they function. Current efforts to better understand how proneural gene function is regulated will not only improve our understanding of neocortical development, but are also critical to the future development of regenerative therapies for the treatment of neuronal degeneration or disease.

Keywords: AS–C; Achaete scute-like 1; Ascl1; BAF; Brahma-associated factors; CGE; GABA(+); GABAergic; GABAergic and glutamatergic neuronal fates; GSK3; HMGA; Hes1; LGE; MGE; NICD; Neurog; Neurog1, Neurog2, Ascl1; Neurogenin; Notch intracellular domain; OPCs; PRC; PcG; PcG repressive complex; RGCs; SP; STAT; SVZ; Signal transducers and activators of transcription; VZ; achaete–scute complex; astrocyte and oligodendrocyte cell fates; bHLH; basic-helix–loop–helix; basic-helix–loop–helix transcription factors; caudal ganglionic eminences; glu(+); glutamatergic; glycogen synthase kinase 3; hairy and enhancer of split 1; high mobility group A; lateral ganglionic eminences; medial ganglionic eminences; neocortex; oligodendrocyte precursor cells; polycomb; proneural genes; radial glial cells; serine–proline; subventricular zone; ventricular zone.