Zeb family members and boundary cap cells underlie developmental plasticity of sensory nociceptive neurons

Dev Cell. 2015 May 4;33(3):343-50. doi: 10.1016/j.devcel.2015.03.021.

Abstract

Dorsal root ganglia (DRG) sensory neurons arise from heterogeneous precursors that differentiate in two neurogenic waves, respectively controlled by Neurog2 and Neurog1. We show here that transgenic mice expressing a Zeb1/2 dominant-negative form (DBZEB) exhibit reduced numbers of nociceptors and altered pain sensitivity. This reflects an early impairment of Neurog1-dependent neurogenesis due to the depletion of specific sensory precursor pools, which is slightly later partially compensated by the contribution of boundary cap cells (BCCs). Indeed, combined DBZEB expression and genetic BCCs ablation entirely deplete second wave precursors and, in turn, nociceptors, thus recapitulating the Neurog1(-/-) neuronal phenotype. Altogether, our results uncover roles for Zeb family members in the developing DRGs; they show that the Neurog1-dependent sensory neurogenesis can be functionally partitioned in two successive phases; and finally, they illustrate plasticity in the developing peripheral somatosensory system supported by the BCCs, thereby providing a rationale for sensory precursor diversity.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Basic Helix-Loop-Helix Transcription Factors / deficiency
  • Basic Helix-Loop-Helix Transcription Factors / metabolism
  • Cell Differentiation / physiology
  • Ganglia, Spinal / embryology
  • Ganglia, Spinal / metabolism
  • Gene Expression Regulation, Developmental
  • Homeodomain Proteins / genetics
  • Homeodomain Proteins / metabolism*
  • Kruppel-Like Transcription Factors / genetics
  • Kruppel-Like Transcription Factors / metabolism*
  • Mice, Transgenic
  • Nerve Tissue Proteins / deficiency
  • Nerve Tissue Proteins / metabolism
  • Neurogenesis / genetics
  • Neurogenesis / physiology
  • Neuronal Plasticity / genetics
  • Neuronal Plasticity / physiology*
  • Nociceptors / metabolism*
  • Repressor Proteins / genetics
  • Repressor Proteins / metabolism*
  • Zinc Finger E-box Binding Homeobox 2
  • Zinc Finger E-box-Binding Homeobox 1

Substances

  • Basic Helix-Loop-Helix Transcription Factors
  • Homeodomain Proteins
  • Kruppel-Like Transcription Factors
  • Nerve Tissue Proteins
  • Repressor Proteins
  • ZEB1 protein, mouse
  • ZEB2 protein, mouse
  • Zinc Finger E-box Binding Homeobox 2
  • Zinc Finger E-box-Binding Homeobox 1
  • Neurog1 protein, mouse