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

Svetlana Tutukova,Luis R Hernandez-Miranda,Victor Tarabykin

doi:10.3389/fnmol.2021.662774

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.

Highlights

The interest to understand the molecular mechanisms that generate our central nervous system has never been greater, as the intensive work of clinicians, neurologists, and developmental biologists demonstrate that several naturally occurring neurological disorders originate from deficits impairing brain development in humans (Ross and Walsh, 2001; Subramanian et al, 2019)
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
In the developing nervous system, the subfamily of neural lineage bHLH transcription factors regulates a variety of biological functions that range from progenitor cell proliferation and survival to neuronal differentiation, neuronal migration, fate specification, axonal navigation, dendritic elongation, and synaptic formation

Summary

INTRODUCTION

The interest to understand the molecular mechanisms that generate our central nervous system has never been greater, as the intensive work of clinicians, neurologists, and developmental biologists demonstrate that several naturally occurring neurological disorders originate from deficits impairing brain development in humans (Ross and Walsh, 2001; Subramanian et al, 2019). These genes encompass most of the neural lineage bHLH transcription factors and are predominantly expressed by differentiated neurons, in which they regulate fate specification and neuronal identity maintenance Members of this group include Neurod, Neurod, Neurod, Bhlhe. The other two members of the Neurod family, Neurod and Neurod, display a highly overlapping expression pattern that appears in the mouse cerebral cortex around embryonic day 12 (Bormuth et al, 2013) Both transcription factors are abundantly expressed by postmitotic pyramidal neurons during embryonic development, albeit their expression levels decline in the postnatal life. Neurod seems to be selectively expressed in a subset of pyramidal neurons, those residing in the deeper layers of the adult mouse cortex; whereas Neurod is expressed by all cortical pyramidal neurons irrespectively of their laminar position (Bormuth et al, 2013)

NEUROD FAMILY IN CORTICAL DEVELOPMENT AND CORTICAL FUNCTION

NEUROD FAMILY IN THE DEVELOPMENT OF THE POSTERIOR NEURAL TUBE

NEUROD GENES IN HUMAN NEUROLOGICAL DISORDERS

CONCLUSION