Key basic helix-loop-helix transcription factor genes Hes1 and Ngn2 are regulated by Pax3 during mouse embryonic development

Hiromichi Nakazaki, Anvesh C. Reddy, Barbara L. Mania-Farnell, Yueh Wei Shen, Shunsuke Ichi, Christopher McCabe, David George, David G. McLone, Tadanori Tomita, C. S.K. Mayanil*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

54 Scopus citations

Abstract

Pax3 is expressed early during embryonic development in spatially restricted domains including limb muscle, neural crest, and neural tube. Pax3 functions at the nodal point in melanocyte stem cell differentiation, cardiogenesis and neurogenesis. Additionally Pax3 has been implicated in migration and differentiation of precursor cell populations. Currently there are questions about how Pax3 regulates these diverse functions. In this study we found that in the absence of functional Pax3, as in Splotch embryos, the neural crest cells undergo premature neurogenesis, as evidenced by increased Brn3a positive staining in neural tube explants, in comparison with wild-type. Premature neurogenesis in the absence of functional Pax3 may be due to a change in the regulation of basic helix-loop-helix transcription factors implicated in proliferation and differentiation. Using promoter-luciferase activity measurements in transient co-transfection experiments and electro-mobility shift assays, we show that Pax3 regulates Hairy and enhancer of split homolog-1 (Hes1) and Neurogenin2 (Ngn2) by directly binding to their promoters. Chromatin immunoprecipitation assays confirmed that Pax3 bound to cis-regulatory elements within Hes1 and Ngn2 promoters. These observations suggest that Pax3 regulates Hes1 and Ngn2 and imply that it may couple migration with neural stem cell maintenance and neurogenesis.

Original languageEnglish (US)
Pages (from-to)510-523
Number of pages14
JournalDevelopmental Biology
Volume316
Issue number2
DOIs
StatePublished - Apr 15 2008

Keywords

  • Chromatin immunoprecipitation
  • Explant cultures
  • Hes1
  • Neural tube
  • Neurogenin2
  • Pax3
  • Premature neurogenesis
  • Promoter
  • Splotch
  • Stem cells

ASJC Scopus subject areas

  • Molecular Biology
  • Developmental Biology
  • Cell Biology

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