Temporal refinement of Dach1 expression contributes to the development of somatosensory neurons

EMBO J. 2025 May;44(10):2882-2905. doi: 10.1038/s44318-025-00427-y. Epub 2025 Apr 9.

Abstract

During somatosensory neurogenesis, neurons are born in an unspecialized transcriptional state. Several transcription factors in these cells follow a broad-to-restricted expression trajectory as development proceeds, giving rise to neuron subtypes with different identities. The relevance of this temporal refinement of transcription factor expression remains unclear as the functions of transcription factors with broad-to-restricted expression patterns have been mostly studied in those neuron subtypes in which they remain active. Here we show that Dach1 encodes a bona fide transcription factor with a broad-to-restricted expression pattern retained and required in tactile somatosensory neurons. In developing nociceptors, Prdm12 contributes to Dach1 silencing. Using genetic approaches to prevent its temporal restriction during mouse somatosensory development, we reveal that Dach1 expression refinement is a prerequisite for the acquisition of an appropriate transcriptional profile in those somatosensory neuron subtypes in which it becomes ultimately silenced. These findings highlight the essential role played by Dach1 during somatosensory neuron development and demonstrate that the temporal pattern of broad-to-restricted expression followed by several transcription factors is physiologically important for the development of somatosensory neurons.

Keywords: Dorsal Root Ganglia; LTMR; Nociceptor; Peripheral Nervous System.

MeSH terms

  • Animals
  • Eye Proteins* / genetics
  • Eye Proteins* / metabolism
  • Gene Expression Regulation, Developmental*
  • Mice
  • Neurogenesis*
  • Neurons* / metabolism
  • Somatosensory Cortex* / cytology
  • Transcription Factors* / genetics
  • Transcription Factors* / metabolism

Substances

  • Dach1 protein, mouse
  • Transcription Factors
  • Eye Proteins