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

36 Citations (Scopus)

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

Fingerprint

Neural Tube
E-Box Elements
Basic Helix-Loop-Helix Transcription Factors
DNA
Nervous System
Transgenic Mice
Cell Differentiation
Carrier Proteins
Stem Cells
Binding Sites
Mutation

Keywords

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

ASJC Scopus subject areas

  • Developmental Biology
  • Cell Biology
  • Molecular Biology

Cite this

Ascl1 and Neurog2 form novel complexes and regulate Delta-like3 (Dll3) expression in the neural tube. / Henke, R. Michael; Meredith, David M.; Borromeo, Mark D.; Savage, Trisha K.; Johnson, Jane E.

In: Developmental Biology, Vol. 328, No. 2, 15.04.2009, p. 529-540.

Research output: Contribution to journalArticle

Henke, R. Michael ; Meredith, David M. ; Borromeo, Mark D. ; Savage, Trisha K. ; Johnson, Jane E. / Ascl1 and Neurog2 form novel complexes and regulate Delta-like3 (Dll3) expression in the neural tube. In: Developmental Biology. 2009 ; Vol. 328, No. 2. pp. 529-540.
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