Basic Helix-Loop-Helix transcription factors cooperate to specify a cortical projection neuron identity

Mattar, Pierre, Langevin, Lisa Marie, Markham, Kathryn, Klenin, Natalia, Shivji, Salma, Zinyk, Dawn and Schuurmans, Carol (2008) Basic Helix-Loop-Helix transcription factors cooperate to specify a cortical projection neuron identity. Molecular and Cellular Biology, 28 5: 1456-1469.


Author Mattar, Pierre
Langevin, Lisa Marie
Markham, Kathryn
Klenin, Natalia
Shivji, Salma
Zinyk, Dawn
Schuurmans, Carol
Title Basic Helix-Loop-Helix transcription factors cooperate to specify a cortical projection neuron identity
Journal name Molecular and Cellular Biology   Check publisher's open access policy
ISSN 0270-7306
1098-5549
Publication date 2008-03
Year available 2007
Sub-type Article (original research)
DOI 10.1128/MCB.01510-07
Volume 28
Issue 5
Start page 1456
End page 1469
Total pages 14
Place of publication Washington, DC, United States
Publisher American Society for Microbiology
Language eng
eng
Subject 1108 Medical Microbiology
Formatted abstract Several transcription factors are essential determinants of a cortical projection neuron identity, but their mode of action (instructive versus permissive) and downstream genetic cascades remain poorly defined. Here, we demonstrate that the proneural basic helix-loop-helix (bHLH) gene Ngn2 instructs a partial cortical identity when misexpressed in ventral telencephalic progenitors, inducing ectopic marker expression in a defined temporal sequence, including early (24 h; Nscl2), intermediate (48 h; BhlhB5), and late (72 h; NeuroD, NeuroD2, Math2, and Tbr1) target genes. Strikingly, cortical gene expression was much more rapidly induced by Ngn2 in the dorsal telencephalon (within 12 to 24 h). We identify the bHLH gene Math3 as a dorsally restricted Ngn2 transcriptional target and cofactor, which synergizes with Ngn2 to accelerate target gene transcription in the cortex. Using a novel in vivo luciferase assay, we show that Ngn2 generates only ~ 60% of the transcriptional drive in ventral versus dorsal telencephalic domains, an activity that is augmented by Math3, providing a mechanistic basis for regional differences in Ngn2 function. Cortical bHLH genes thus cooperate to control transcriptional strength, thereby temporally coordinating downstream gene expression.
Q-Index Code C1
Q-Index Status Provisional Code
Institutional Status Non-UQ
Additional Notes Published ahead of print on 26 December 2007.

Document type: Journal Article
Sub-type: Article (original research)
Collections: Excellence in Research Australia (ERA) - Collection
School of Biomedical Sciences Publications
 
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