Autoregulation and multiple enhancers control Math1 expression in the developing nervous system

Amy W. Helms, Andrew L. Abney, Nissim Ben-Arie, Huda Y. Zoghbi, Jane E. Johnson

Research output: Contribution to journalArticle

222 Scopus citations

Abstract

Development of the vertebrate nervous system requires the actions of transcription factors that establish regional domains of gene expression, which results in the generation of diverse neuronal cell types. MATH1, a transcription factor of the bHLH class, is expressed during development of the nervous system in multiple neuronal domains, including the dorsal neural tube, the EGL of the cerebellum and the hair cells of the vestibular and auditory systems. MATH1 is essential for proper development of the granular layer of the cerebellum and the hair cells of the cochlear and vestibular systems, as shown in mice carrying a targeted disruption of Math1. Previously, we showed that 21 kb of sequence flanking the Math1-coding region is sufficient for Math1 expression in transgenic mice. Here we identify two discrete sequences within the 21 kb region that are conserved between mouse and human, and are sufficient for driving a lacZ reporter gene in these domains of Math1 expression in transgenic mice. The two identified enhancers, while dissimilar in sequence, appear to have redundant activities in the different Math1 expression domains except the spinal neural tube. The regulatory mechanisms for each of the diverse Math1 expression domains are tightly linked, as separable regulatory elements for any given domain of Math1 expression were not found, suggesting that a common regulatory mechanism controls these apparently unrelated domains of expression. In addition, we demonstrate a role for autoregulation in controlling the activity of the Math1 enhancer, through an essential E-box consensus binding site.

Original languageEnglish (US)
Pages (from-to)1185-1196
Number of pages12
JournalDevelopment
Volume127
Issue number6
StatePublished - Mar 1 2000

Keywords

  • Cerebellum
  • EGL
  • Ear
  • Merkel cell
  • Neural development
  • Sensory epithelium
  • Transcription factor
  • Whisker vibrissae
  • bHLH

ASJC Scopus subject areas

  • Molecular Biology
  • Developmental Biology

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  • Cite this

    Helms, A. W., Abney, A. L., Ben-Arie, N., Zoghbi, H. Y., & Johnson, J. E. (2000). Autoregulation and multiple enhancers control Math1 expression in the developing nervous system. Development, 127(6), 1185-1196.