The Role of Neurod Genes in Brain Development, Function, and Disease

Abstract

Transcriptional regulation is essential for the correct functioning of cells during development and in postnatal life. The basic Helix-loop-Helix (bHLH) superfamily of transcription factors is well conserved throughout evolution and plays critical roles in tissue development and tissue maintenance. A subgroup of this family, called neural lineage bHLH factors, is critical in the development and function of the central nervous system. In this review, we will focus on the function of one subgroup of neural lineage bHLH factors, the Neurod family. The Neurod family has four members: Neurod1, Neurod2, Neurod4, and Neurod6. Available evidence shows that these four factors are key during the development of the cerebral cortex but also in other regions of the central nervous system, such as the cerebellum, the brainstem, and the spinal cord. We will also discuss recent reports that link the dysfunction of these transcription factors to neurological disorders in humans.

Keywords: bHLH factor; brain development; neurod family; neurological diseases; transcription factors.

Figure 1

Developmental expression of the Neurod family during cortical development of mice. (A) Schematic representation of the cortical development in mice. (Left) During early cortical development, neural progenitor cells (light green, also called radial glial cells) located in the dorsal ventricular zone (VZ) make early decisions as to self-renew or differentiate into early born neurons (light blue). (Middle) As cortical development progress, neuronal progenitor cells increase their choices and can then self-renew or differentiate into more committed progenitors (light orange) that populate an emerging subventricular zone (SVZ) or into differentiated neurons (light blue). Upon differentiation, neurons radially migrate throughout an intermediate zone (IZ) in order to populate the developing cortical plate (gray areas), using radial glial fibers as a scaffold. (Right) According to the time of birth, cortical pyramidal neurons (dark blue) settle into their appropriate cortical layer and start the elaboration of dendritic trees and the elongation or their axonal processes (see text). (B) Schematic display of the expression pattern exhibited by the different members of the Neurod family during cortical development (see text). (C) Table summarizing the known functions of the different members of the Neurod family during cortical development (see text). Panel (A) is inspired from Guo et al. (2015).