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

Dev Biol. 2009 Apr 15;328(2):529-40. doi: 10.1016/j.ydbio.2009.01.007. Epub 2009 Jan 14.


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.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Base Sequence
  • Basic Helix-Loop-Helix Transcription Factors / genetics
  • Basic Helix-Loop-Helix Transcription Factors / physiology*
  • Binding Sites
  • Dimerization
  • E-Box Elements
  • Gene Expression Regulation, Developmental
  • Intracellular Signaling Peptides and Proteins / genetics
  • Intracellular Signaling Peptides and Proteins / physiology*
  • Membrane Proteins / genetics
  • Membrane Proteins / physiology*
  • Mice
  • Mice, Transgenic
  • Molecular Sequence Data
  • Mutation
  • Nerve Tissue Proteins / genetics
  • Nerve Tissue Proteins / physiology*
  • Neural Tube / embryology
  • Neural Tube / physiology*
  • Neurons / physiology
  • Promoter Regions, Genetic
  • Stem Cells / physiology


  • Ascl1 protein, mouse
  • Basic Helix-Loop-Helix Transcription Factors
  • Dll3 protein, mouse
  • Intracellular Signaling Peptides and Proteins
  • Membrane Proteins
  • Nerve Tissue Proteins
  • Neurog2 protein, mouse