GABAergic Differentiation Induced by Mash1 Is Compromised by the bHLH Proteins Neurogenin2, NeuroD1, and NeuroD2.
(2010) In Cerebral Cortex 20. p.1234-1244- 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... (More)
- 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. (Less)
Please use this url to cite or link to this publication:
https://lup.lub.lu.se/record/1483303
- author
- Roybon, Laurent LU ; Mastracci, Teresa L ; Ribeiro, Diogo ; Sussel, Lori ; Brundin, Patrik LU and Li, Jia-Yi LU
- organization
- publishing date
- 2010
- type
- Contribution to journal
- publication status
- published
- subject
- in
- Cerebral Cortex
- volume
- 20
- pages
- 1234 - 1244
- publisher
- Oxford University Press
- external identifiers
-
- wos:000276736000022
- pmid:19767311
- scopus:77951121610
- pmid:19767311
- ISSN
- 1460-2199
- DOI
- 10.1093/cercor/bhp187
- language
- English
- LU publication?
- yes
- additional info
- The information about affiliations in this record was updated in December 2015. The record was previously connected to the following departments: Neuronal Survival (013212041), Neural Plasticity and Repair (013210080)
- id
- f753a341-deee-469f-8074-b6738b473369 (old id 1483303)
- alternative location
- http://www.ncbi.nlm.nih.gov/pubmed/19767311?dopt=Abstract
- date added to LUP
- 2016-04-04 07:29:10
- date last changed
- 2022-02-28 03:40:43
@article{f753a341-deee-469f-8074-b6738b473369, 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.}}, author = {{Roybon, Laurent and Mastracci, Teresa L and Ribeiro, Diogo and Sussel, Lori and Brundin, Patrik and Li, Jia-Yi}}, issn = {{1460-2199}}, language = {{eng}}, pages = {{1234--1244}}, publisher = {{Oxford University Press}}, series = {{Cerebral Cortex}}, title = {{GABAergic Differentiation Induced by Mash1 Is Compromised by the bHLH Proteins Neurogenin2, NeuroD1, and NeuroD2.}}, url = {{http://dx.doi.org/10.1093/cercor/bhp187}}, doi = {{10.1093/cercor/bhp187}}, volume = {{20}}, year = {{2010}}, }