Function of Proneural Genes Ascl1 and Asense in Neurogenesis: How Similar Are They?

Diogo S Soares,Diogo S Castro,Catarina C.F Homem

doi:10.3389/fcell.2022.838431

Abstract

Proneural genes were initially identified in Drosophila, where pioneer work on these important regulators of neural development was performed, and from which the term proneural function was coined. Subsequently, their counterparts in vertebrates were identified, and their function in neural development extensively characterized. The function of proneural transcription factors in flies and vertebrates is, however, very distinct. In flies, proneural genes play an early role in neural induction, by endowing neural competence to ectodermal cells. In contrast, vertebrate proneural genes are expressed only after neural specification, in neural stem and progenitor cells, where they play key regulatory functions in quiescence, proliferation, and neuronal differentiation. An exception to this scenario is the Drosophila proneural gene asense, which has a late onset of expression in neural stem cells of the developing embryo and larvae, similar to its vertebrate counterparts. Although the role of Asense remains poorly investigated, its expression pattern is suggestive of functions more in line with those of vertebrate proneural genes. Here, we revise our current understanding of the multiple activities of Asense and of its closest vertebrate homologue Ascl1 in neural stem/progenitor cell biology, and discuss possible parallels between the two transcription factors in neurogenesis regulation.

Highlights

In the developing nervous system, the specification and differentiation of neuronal cells relies on a class of proneural genes that encode basic-helix-loop-helix transcription factors (Huang et al, 2014)
The pivotal role of Ascl1 in vertebrate neurogenesis has been extensively characterized in recent years
Neither Ase or Ascl1 are required for the early acquisition of neural stem (NS) cell identity, playing instead later regulatory roles associated with their expression in NS cells, and some of their progeny

Summary

INTRODUCTION

In the developing nervous system, the specification and differentiation of neuronal cells relies on a class of proneural genes that encode basic-helix-loop-helix (bHLH) transcription factors (Huang et al, 2014). In the SVZ of the lateral ventricle, Ascl protein is detected in rapidly proliferating transit amplifying progenitors (TAPs) and in a small fraction of neuroblasts, migrating towards the olfactory bulb (Parras et al, 2004) This suggests the dual role of Ascl (promoting sequentially proliferation and differentiation) is maintained in the adult, where its pro-proliferative function is less redundant with other pathways as compared to embryonic stages (Casarosa et al, 1999; Andersen et al, 2014). Type I NBs, in both the central brain and ventral nerve cord, divide asymmetrically to self-renew, and produce a smaller Ganglion Mother Cell (GMC) that subsequently divides terminally into two neurons or glia These NBs are characterized by the expression of Ase, along with nuclear Deadpan (Dpn), and cytoplasmic Prospero (Pros). Whether Ase plays a role similar to Ascl in promoting exit from quiescence, remains undetermined

A Quantitative Model of Ascl1 Function

A Cell-Autonomous Cross-Talk With the Notch Pathway

CONCLUSION