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First published online November 26, 2007
doi: 10.1242/10.1242/dev.009118

Development 134, 4405-4415 (2007)
Published by The Company of Biologists 2007
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Cross-regulation of Ngn1 and Math1 coordinates the production of neurons and sensory hair cells during inner ear development

Steven Raft1, Edmund J. Koundakjian2, Herson Quinones3, Chathurani S. Jayasena1, Lisa V. Goodrich2, Jane E. Johnson3, Neil Segil1,4,* and Andrew K. Groves1,4,*

1 Gonda Department of Cell and Molecular Biology, House Ear Institute, 2100 West 3rd Street, Los Angeles CA 90057, USA.
2 Department of Neurobiology, Harvard Medical School, 220 Longwood Avenue, Boston, MA 02115, USA.
3 Center for Basic Neuroscience, UT Southwestern Medical Center, Dallas, TX 75390, USA.
4 Department of Cell and Neurobiology, Keck School of Medicine, University of Southern California, Los Angeles, CA 90033, USA.

* Authors for correspondence (e-mails: nsegil{at}hei.org; agroves{at}hei.org)

Accepted 19 September 2007

Temporal and spatial coordination of multiple cell fate decisions is essential for proper organogenesis. Here, we define gene interactions that transform the neurogenic epithelium of the developing inner ear into specialized mechanosensory receptors. By Cre-loxP fate mapping, we show that vestibular sensory hair cells derive from a previously neurogenic region of the inner ear. The related bHLH genes Ngn1 (Neurog1) and Math1 (Atoh1) are required, respectively, for neural and sensory epithelial development in this system. Our analysis of mouse mutants indicates that a mutual antagonism between Ngn1 and Math1 regulates the transition from neurogenesis to sensory cell production during ear development. Furthermore, we provide evidence that the transition to sensory cell production involves distinct autoregulatory behaviors of Ngn1 (negative) and Math1 (positive). We propose that Ngn1, as well as promoting neurogenesis, maintains an uncommitted progenitor cell population through Notch-mediated lateral inhibition, and Math1 irreversibly commits these progenitors to a hair-cell fate.

Key words: Proneural gene, bHLH, Hair cells, Inner ear, Otocyst, Neurogenesis


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