Vsx1 and Chx10 paralogs sequentially secure V2 interneuron identity during spinal cord development

Stéphanie Debrulle, Charlotte Baudouin, Maria Hidalgo-Figueroa, Barbara Pelosi, Cédric Francius, Vincent Rucchin, Kara Ronellenfitch, Robert L. Chow, Fadel Tissir, Soo Kyung Lee, Frédéric Clotman

Research output: Contribution to journalArticle

2 Scopus citations

Abstract

Paralog factors are usually described as consolidating biological systems by displaying redundant functionality in the same cells. Here, we report that paralogs can also cooperate in distinct cell populations at successive stages of differentiation. In mouse embryonic spinal cord, motor neurons and V2 interneurons differentiate from adjacent progenitor domains that share identical developmental determinants. Therefore, additional strategies secure respective cell fate. In particular, Hb9 promotes motor neuron identity while inhibiting V2 differentiation, whereas Chx10 stimulates V2a differentiation while repressing motor neuron fate. However, Chx10 is not present at the onset of V2 differentiation and in other V2 populations. In the present study, we show that Vsx1, the single paralog of Chx10, which is produced earlier than Chx10 in V2 precursors, can inhibit motor neuron differentiation and promote V2 interneuron production. However, the single absence of Vsx1 does not impact on V2 fate consolidation, suggesting that lack of Vsx1 may be compensated by other factors. Nevertheless, Vsx1 cooperates with Chx10 to prevent motor neuron differentiation in early V2 precursors although these two paralog factors are not produced in the same cells. Hence, this study uncovers an original situation, namely labor division, wherein paralog genes cooperate at successive steps of neuronal development.

Original languageEnglish (US)
Pages (from-to)4117-4131
Number of pages15
JournalCellular and Molecular Life Sciences
Volume77
Issue number20
DOIs
StatePublished - Oct 1 2020

Keywords

  • Chx10
  • Motor neurons
  • Paralog genes
  • Spinal cord
  • V2 interneurons
  • Vsx1

ASJC Scopus subject areas

  • Molecular Medicine
  • Molecular Biology
  • Pharmacology
  • Cellular and Molecular Neuroscience
  • Cell Biology

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  • Cite this

    Debrulle, S., Baudouin, C., Hidalgo-Figueroa, M., Pelosi, B., Francius, C., Rucchin, V., Ronellenfitch, K., Chow, R. L., Tissir, F., Lee, S. K., & Clotman, F. (2020). Vsx1 and Chx10 paralogs sequentially secure V2 interneuron identity during spinal cord development. Cellular and Molecular Life Sciences, 77(20), 4117-4131. https://doi.org/10.1007/s00018-019-03408-7