Vsx1 and Chx10 paralogs sequentially secure V2 interneuron identity during spinal cord development
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Cellular and Molecular Life Sciences
ORIGINAL ARTICLE
Vsx1 and Chx10 paralogs sequentially secure V2 interneuron identity during spinal cord development Stéphanie Debrulle1 · Charlotte Baudouin1 · Maria Hidalgo‑Figueroa1,4 · Barbara Pelosi1 · Cédric Francius1,5 · Vincent Rucchin1 · Kara Ronellenfitch2 · Robert L. Chow2 · Fadel Tissir1 · Soo‑Kyung Lee3 · Frédéric Clotman1 Received: 14 June 2019 / Revised: 28 November 2019 / Accepted: 28 November 2019 © Springer Nature Switzerland AG 2019
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. Keywords Paralog genes · Vsx1 · Chx10 · V2 interneurons · Motor neurons · Spinal cord
Introduction
Electronic supplementary material The online version of this article (https://doi.org/10.1007/s00018-019-03408-7) contains supplementary material, which is available to authorized users. * Frédéric Clotman [email protected] 1
Université Catholique de Louvain, Institute of Neuroscience, Brussels, Belgium
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Department of Biology, University of Victoria, Victoria, Canada
3
Oregon Health and Science University, Papé Family Pediatric Research Institute and Vollum Institute, Portland, USA
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Present Address: Neuropsychopharmacology and Psychobiology Research Group, Area of Psychobiology, Department of Psychology, Instituto de Investigación E Innovación en Ciencias Biomédicas de Cádiz (INiBICA), University of Cadiz, Cadiz, Spain
5
Present Address: PAREXEL International, Paris, France
Robustness of a biological system is defined as the ability to maintain its functions despite perturbations. The mechanistic bases of robustness are not fully understood but seem to notably rely on the fact that several genes or
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