Ascl1 and Neurog2 form novel complexes and regulate Delta-like3 (Dll3) expression in the neural tube

R. Michael Henke, David M. Meredith, Mark D. Borromeo, Trisha K. Savage, Jane E. Johnson

Research output: Contribution to journalArticle

46 Scopus citations

Abstract

Delta-like 3 (Dll3) is a Delta family member expressed broadly in the developing nervous system as neural progenitor cells initiate differentiation. A proximal promoter sequence for Dll3 is conserved across multiple species and is sufficient to direct GFP expression in a Dll3-like pattern in the neural tube of transgenic mice. This promoter contains multiple E-boxes, the consensus binding site for bHLH factors. Dll3 expression and the activity of the Dll3-promoter in the dorsal neural tube depends on the basic helix-loop-helix (bHLH) transcription factors Ascl1 (Mash1) and Neurog2 (Ngn2). Mutations in each E-box identified in the Dll3-promoter allowed distinct enhancer or repressor properties to be assigned to each site individually or in combination. In addition, each E-box has distinct characteristics relative to binding of bHLH factors Ascl1, Neurog1, and Neurog2. Surprisingly, novel Ascl1 containing DNA binding complexes are identified that interact with specific E-box sites within the Dll3-promoter in vitro. These complexes include Ascl1/Ascl1 homodimers and Ascl1/Neurog2 heterodimers, complexes that in some cases require additional undefined factors for efficient DNA binding. Thus, a complex interplay of E-box binding proteins spatially and temporally regulate Dll3 levels during neural tube development.

Original languageEnglish (US)
Pages (from-to)529-540
Number of pages12
JournalDevelopmental Biology
Volume328
Issue number2
DOIs
StatePublished - Apr 15 2009

Keywords

  • Delta
  • Dorsal spinal cord development
  • Gene regulation
  • Mash1
  • Neurogenin
  • Notch ligands
  • bHLH transcription factors

ASJC Scopus subject areas

  • Molecular Biology
  • Developmental Biology
  • Cell Biology

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