Cross-regulation of Ngn1 and Math1 coordinates the production of neurons and sensory hair cells during inner ear development

Steven Raft, Edmund J. Koundakjian, Herson Quinones, Chathurani S. Jayasena, Lisa V. Goodrich, Jane E. Johnson, Neil Segil, Andrew K. Groves

Research output: Contribution to journalArticle

149 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)4405-4415
Number of pages11
JournalDevelopment
Volume134
Issue number24
DOIs
StatePublished - Dec 1 2007

Keywords

  • Hair cells
  • Inner ear
  • Neurogenesis
  • Otocyst
  • Proneural gene
  • bHLH

ASJC Scopus subject areas

  • Molecular Biology
  • Developmental Biology

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    Raft, S., Koundakjian, E. J., Quinones, H., Jayasena, C. S., Goodrich, L. V., Johnson, J. E., Segil, N., & Groves, A. K. (2007). Cross-regulation of Ngn1 and Math1 coordinates the production of neurons and sensory hair cells during inner ear development. Development, 134(24), 4405-4415. https://doi.org/10.1242/dev.009118