Cerebrospinal fluid-derived Semaphorin3B orients neuroepithelial cell divisions in the apicobasal axis

Elise Arbeille, Florie Reynaud, Isabelle Sanyas, Muriel Bozon, Karine Kindbeiter, Frédéric Causeret, Alessandra Pierani, Julien Falk, Frédéric Moret and Valérie Castellani ()
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Elise Arbeille: University of Lyon, University of Lyon1, CGΦMC, UMR CNRS 5534
Florie Reynaud: University of Lyon, University of Lyon1, CGΦMC, UMR CNRS 5534
Isabelle Sanyas: University of Lyon, University of Lyon1, CGΦMC, UMR CNRS 5534
Muriel Bozon: University of Lyon, University of Lyon1, CGΦMC, UMR CNRS 5534
Karine Kindbeiter: University of Lyon, University of Lyon1, CGΦMC, UMR CNRS 5534
Frédéric Causeret: CNRS UMR 7592, Institut Jacques Monod, University Paris Diderot, Sorbonne Paris Cité
Alessandra Pierani: CNRS UMR 7592, Institut Jacques Monod, University Paris Diderot, Sorbonne Paris Cité
Julien Falk: University of Lyon, University of Lyon1, CGΦMC, UMR CNRS 5534
Frédéric Moret: University of Lyon, University of Lyon1, CGΦMC, UMR CNRS 5534
Valérie Castellani: University of Lyon, University of Lyon1, CGΦMC, UMR CNRS 5534

Nature Communications, 2015, vol. 6, issue 1, 1-14

Abstract: Abstract The spatial orientation of cell divisions is fundamental for tissue architecture and homeostasis. Here we analysed neuroepithelial progenitors in the developing mouse spinal cord to determine whether extracellular signals orient the mitotic spindle. We report that Semaphorin3B (Sema3B) released from the floor plate and the nascent choroid plexus in the cerebrospinal fluid (CSF) controls progenitor division orientation. Delivery of exogenous Sema3B to neural progenitors after neural tube opening in living embryos promotes planar orientation of their division. Preventing progenitor access to cues present in the CSF by genetically engineered canal obstruction affects the proportion of planar and oblique divisions. Sema3B knockout phenocopies the loss of progenitor access to the CSF. Sema3B binds to the apical surface of mitotic progenitors and exerts its effect via Neuropilin receptors, GSK3 activation and subsequent inhibition of the microtubule stabilizer CRMP2. Thus, extrinsic control mediated by the Semaphorin signalling orients progenitor divisions in neurogenic zones.

Date: 2015
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DOI: 10.1038/ncomms7366

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