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Sequential roles for Mash1 and Ngn2 in the generation of dorsal spinal cord interneurons.

The dorsal spinal cord contains a diverse array of neurons that connect sensory input from the periphery to spinal cord motoneurons and brain. During development, six dorsal neuronal populations (dI1-dI6) have been defined by expression of homeodomain factors and position in the dorsoventral axis. The bHLH transcription factors Mash1 and Ngn2 have distinct roles in specification of these neurons. Mash1 is necessary and sufficient for generation of most dI3 and all dI5 neurons. Unexpectedly, dI4 neurons are derived from cells expressing low levels or no Mash1, and this population increases in the Mash1 mutant. Ngn2 is not required for any specific neuronal cell type but appears to modulate the composition of neurons that form. In the absence of Ngn2, there is an increase in the number of dI3 and dI5 neurons, in contrast to the effects produced by activity of Mash1. Mash1 is epistatic to Ngn2, and, unlike the relationship between other neural bHLH factors, cross-repression of expression is not detected. Thus, bHLH factors, particularly Mash1 and related family members Math1 and Ngn1, provide a code for generating neuronal diversity in the dorsal spinal cord with Ngn2 serving to modulate the number of neurons in each population formed.

Pubmed ID: 15901662


  • Helms AW
  • Battiste J
  • Henke RM
  • Nakada Y
  • Simplicio N
  • Guillemot F
  • Johnson JE


Development (Cambridge, England)

Publication Data

June 2, 2005

Associated Grants

  • Agency: NICHD NIH HHS, Id: R01 HD 37932
  • Agency: NICHD NIH HHS, Id: R01 HD037932
  • Agency: NINDS NIH HHS, Id: R01 NS 32817
  • Agency: NINDS NIH HHS, Id: R01 NS032817

Mesh Terms

  • Animals
  • Basic Helix-Loop-Helix Transcription Factors
  • Body Patterning
  • Cell Differentiation
  • DNA-Binding Proteins
  • Epistasis, Genetic
  • Interneurons
  • Mice
  • Mice, Knockout
  • Nerve Tissue Proteins
  • Spinal Cord
  • Transcription Factors