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GABAergic Differentiation Induced by Mash1 Is Compromised by the bHLH Proteins Neurogenin2, NeuroD1, and NeuroD2

Roybon, Laurent, Mastracci, Teresa L., Ribeiro, Diogo, Sussel, Lori, Brundin, Patrik, Li, Jia-Yi·2010·Cerebral Cortex
DOI 10.1093/cercor/bhp187
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Abstract

During forebrain development, Mash1 directs gamma-aminobutyric acid (GABA)ergic neuron differentiation ventrally in the ganglionic eminences. Repression of Mash1 in the cortex is necessary to prevent the formation of GABAergic interneurons. Negative regulation of Mash1 has been attributed to members of the Neurogenin family; the genetic ablation of Neurogenin2 (Ngn2) leads to the derepression of Mash1 and the formation of ectopic GABAergic neurons in the cortex. We have developed an in vitro system to clarify the importance of NeuroD proteins in the Mash1 regulatory pathway. Using a neurosphere culture system, we show that the downstream effectors of the Ngn2 pathway NeuroD1 and NeuroD2 can abrogate GABAergic differentiation directed by Mash1. The ectopic expression of either of these genes in Mash1-expressing cells derived from the lateral ganglionic eminence, independently downregulate Mash1 expression without affecting expression of distal less homeodomain genes. This results in a complete loss of the GABAergic phenotype. Moreover, we demonstrate that ectopic expression of Mash1 in cortical progenitors is sufficient to phenocopy the loss of Ngn2 and strongly enhances ectopic GABAergic differentiation. Collectively, our results define the compensatory and cross-regulatory mechanisms that exist among basic helix-loop-helix transcription factors during neuronal fate specification.

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  • Overexpression of Ngn2 and Sox11 promotes differentiation of primary fibroblasts into cholinergic neurons, whereas it inhibits GABAergic neuronal differentiation.

    “It is known that overexpression of Ngn2 and Sox11 (another transcription factor involved in neuronal induction during embryonic development) promote the differentiation of primary fibroblasts into cholinergic neurons, whereas they inhibits GABAergic neuronal differentiation [35].”

    From USP8 Down-Regulation Promotes Parkin-Independent Mitophagy in the Drosophila Brain and in Human Neurons (2023) · cites this paper as [35]

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Metadata

Authors
Roybon, L., Mastracci, T. L., Ribeiro, D., Sussel, L., Brundin, P., & Li, J.-Y.
Venue
Cerebral Cortex
Publisher
Oxford University Press (OUP)
Published
2009-09-18
Volume
20
Issue
5
Pages
1234-1244
ISSN
  • 1460-2199
  • 1047-3211
DOI
10.1093/cercor/bhp187
Cited by
71
References
1
Language
en

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