Zic1 represses Math1 expression via interactions with the Math1 enhancer and modulation of Math1 autoregulation

Philip J. Ebert, John R. Timmer, Yuji Nakada, Amy W. Helms, Preeti B. Parab, Ying Liu, Thomas L. Hunsaker, Jane E. Johnson

Research output: Contribution to journalReview article

78 Scopus citations

Abstract

Math1 is a basic helix-loop-helix transcription factor expressed in progenitor cells that give rise to dorsal commissural interneurons in the spinal cord, granule cells of the cerebellum, and sensory cells in the inner ear and skin. Transcriptional regulation of this gene is tightly controlled both temporally and spatially during nervous system development. The signals that mediate this regulation are likely integrated at the Math1 enhancer, which is highly conserved among vertebrate species. We have identified the zinc-finger transcription factor Zic1 as a regulator of Math1 expression. Zic1 binds a novel conserved site within the Math1 enhancer, and represses both the expression of endogenous Cath1 (chicken homolog of Math1) and the activity of a Math1 enhancer driven lacZ reporter when expressed in chick neural tubes. Repression by Zic1 blocks the autoregulatory activity of Math1 itself. Although previous reports have shown that Zic1 and Math1 are both induced by BMP signaling, these genes appear to have opposing functions, as Math1 acts to promote neuronal differentiation in the chick neural tube and excess Zic1 appears to block differentiation. Zic1-mediated repression of Cath1 transcription may modulate the temporal switch between the progenitor state and differentiating dorsal cell types during neural tube development.

Original languageEnglish (US)
Pages (from-to)1949-1959
Number of pages11
JournalDevelopment
Volume130
Issue number9
DOIs
StatePublished - May 1 2003

Keywords

  • Chick electroporation
  • Dorsal spinal cord development
  • Mash1/Cash1
  • Math1/Cath1
  • Neuronal differentiation
  • Ngn1
  • Ngn2
  • Transcription repressors
  • Transcriptional regulation
  • bHLH trascription factors

ASJC Scopus subject areas

  • Molecular Biology
  • Developmental Biology

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    Ebert, P. J., Timmer, J. R., Nakada, Y., Helms, A. W., Parab, P. B., Liu, Y., Hunsaker, T. L., & Johnson, J. E. (2003). Zic1 represses Math1 expression via interactions with the Math1 enhancer and modulation of Math1 autoregulation. Development, 130(9), 1949-1959. https://doi.org/10.1242/dev.00419