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First published online 23 March 2005
doi: 10.1242/dev.01781

Development 132, 2147-2155 (2005)
Published by The Company of Biologists 2005
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Commissural neuron identity is specified by a homeodomain protein, Mbh1, that is directly downstream of Math1

Rie Saba1, Jane E. Johnson2 and Tetsuichiro Saito1,*,{dagger}

1 Department of Development and Differentiation, Institute for Frontier Medical Sciences, Kyoto University, Kyoto 606-8507, Japan
2 Center for Basic Neuroscience, University of Texas Southwestern Medical Center, 5323 Harry Hines Boulevard, Dallas, TX 75390-9111, USA

{dagger} Author for correspondence (e-mail: tesaito{at}frontier.kyoto-u.ac.jp)

Accepted 11 February 2005

Proneural basic helix-loop-helix (bHLH) proteins are key regulators of neurogenesis. However, downstream target genes of the bHLH proteins remain poorly defined. Mbh1 confers commissural neuron identity in the spinal cord. Enhancer analysis using transgenic mice revealed that Mbh1 expression required an E-box 3' of the Mbh1 gene. Mbh1 expression was lost in Math1 knockout mice, whereas misexpression of Math1 induced ectopic expression of Mbh1. Moreover, Math1 bound the Mbh1 enhancer containing the E-box in vivo and activated gene expression. Generation of commissural neurons by Math1 was inhibited by a dominant negative form of Mbh1. These findings indicate that Mbh1 is necessary and sufficient for the specification of commissural neurons, as a direct downstream target of Math1.

Key words: Math1 (Atoh1), Proneural, Mbh1 (Barhl2), Homeobox, Spinal cord, Mouse




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