BARHL2 transcription factor regulates the ipsilateral/ contralateral subtype divergence in postmitotic dI1 neurons of the developing spinal cord

Qian Ding, Pushkar S. Joshi, Zheng Hua Xie, Mengqing Xiang, Lin Gan

Research output: Contribution to journalArticle

21 Scopus citations

Abstract

In the dorsal spinal cord, distinct interneuron classes relay specific somatosensory information, such as touch, heat, and pain, from the periphery to higher brain centers via ipsilateral and contralateral axonal pathways. The transcriptional mechanisms by which dorsal interneurons choose between ipsilateral and contralateral projection fates are unknown. Here, we show that a single transcription factor (TF), BARHL2, regulates this choice in proprioceptive dI1 interneurons by selectively suppressing cardinal dI1contra features in dI1ipsi neurons, despite expression by both subtypes. Strikingly, dI1ipsi neurons in Barhl2-null mice exhibit a dI1contra cell settling pattern in the medial deep dorsal horn, and, most importantly, they project axons contralaterally. These aberrations are preceded by ectopic dI1ipsi expression of the defining dI1contra TF, LHX2, and down-regulation of the dI1ipsi-enriched TF, BARHL1. Taken together, these results elucidate BARHL2 as a critical postmitotic regulator of dI1 subtype diversification, as well as its intermediate position in the dI1 genetic hierarchy.

Original languageEnglish (US)
Pages (from-to)1566-1571
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume109
Issue number5
DOIs
StatePublished - Jan 31 2012

Keywords

  • Atoh1/Math1
  • BarH/BarH-like
  • Neurogenesis
  • Neuronal differentiation
  • Robo3/Rig1

ASJC Scopus subject areas

  • General

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