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

First Author  Debrulle S Year  2020
Journal  Cell Mol Life Sci Volume  77
Issue  20 Pages  4117-4131
PubMed ID  31822965 Mgi Jnum  J:299679
Mgi Id  MGI:6471279 Doi  10.1007/s00018-019-03408-7
Citation  Debrulle S, et al. (2020) Vsx1 and Chx10 paralogs sequentially secure V2 interneuron identity during spinal cord development. Cell Mol Life Sci 77(20):4117-4131
abstractText  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.
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