NeuroD1 induces terminal neuronal differentiation in olfactory neurogenesis

Abstract

After their generation and specification in periventricular regions, neuronal precursors maintain an immature and migratory state until their arrival in the respective target structures. Only here are terminal differentiation and synaptic integration induced. Although the molecular control of neuronal specification has started to be elucidated, little is known about the factors that control the latest maturation steps. We aimed at identifying factors that induce terminal differentiation during postnatal and adult neurogenesis, thereby focusing on the generation of periglomerular interneurons in the olfactory bulb. We isolated neuronal precursors and mature neurons from the periglomerular neuron lineage and analyzed their gene expression by microarray. We found that expression of the bHLH transcription factor NeuroD1 strikingly coincides with terminal differentiation. Using brain electroporation, we show that overexpression of NeuroD1 in the periventricular region in vivo leads to the rapid appearance of cells with morphological and molecular characteristics of mature neurons in the subventricular zone and rostral migratory stream. Conversely, shRNA-induced knockdown of NeuroD1 inhibits terminal neuronal differentiation. Thus, expression of a single transcription factor is sufficient to induce neuronal differentiation of neural progenitors in regions that normally do not show addition of new neurons. These results suggest a considerable potential of NeuroD1 for use in cell-therapeutic approaches in the nervous system. adult neurogenesis | bHLH transcription factor | interneurons | postnatal electroporation

Prospero-related homeobox 1 gene (Prox1) is regulated by canonical Wnt signaling and has a stage-specific role in adult hippocampal neurogenesis

“…Our data suggest that similar events take place on the Prox1 enhancer region, given the repression of SOX9 on β-catenin-induced activation in luciferase reporter constructs containing parts of the Prox1 enhancer region. Notably, NeuroD1 is also required for the generation of certain olfactory neurons (11,13,14). Thus, the data presented here add an important piece to the transcriptional mechanisms What could be the downstream targets of Prox1 that are important for neuronal differentiation in vitro and in vivo?…”

“…Recently, it has been shown that NeuroD1, a basic helix-loop-helix transcription factor required for granule cell genesis in the embryonic and adult DG, is regulated by β-catenin-dependent signaling (9)(10)(11)(12). However, NeuroD1 is not only important for hippocampal neurogenesis but is also involved in the generation of SVZ-derived olfactory neurons (11,13,14). Thus, the network of genes regulated by the Wnt pathway to selectively generate DG granule cells in the adult hippocampus remains unknown.…”

A Homozygous Missense Mutation in NEUROD1 Is Associated With Nonsyndromic Autosomal Recessive Retinitis Pigmentosa

“…20,21 NEUROD1 has been shown to play critical roles in multiple biological processes including endocrine cell development, neurogenesis, and glucose homeostasis. [22][23][24][25][26] Several reports associate NEUROD1 mutations with human genetic disease, though almost all of these reports have focused on diabetes. Heterozygous LOF mutations in NEUROD1 can cause autosomal dominant type 2 diabetes.…”

Role of DNMT3B in the regulation of early neural and neural crest specifiers

“…2B). NEUROD1, a basichelix-loop-helix (bHLH) transcription factor normally implicated in the regulation of later stages of neuronal differentiation, including terminal neuronal differentiation in olfactory neurogenesis, [47][48][49][50] showed substantial expression at d12 (Fig. 2A).…”