title: Cerebrospinal fluid-derived Semaphorin3B orients neuroepithelial cell divisions in the apicobasal axis.
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.
authors.affiliation: University of Lyon, University of Lyon1, CGΦMC, UMR CNRS 5534, F-69100 Villeurbanne, France.
authors.forename: Elise
authors.initials: E
authors.lastname: Arbeille
authors.affiliation: University of Lyon, University of Lyon1, CGΦMC, UMR CNRS 5534, F-69100 Villeurbanne, France.
authors.forename: Florie
authors.initials: F
authors.lastname: Reynaud
authors.affiliation: University of Lyon, University of Lyon1, CGΦMC, UMR CNRS 5534, F-69100 Villeurbanne, France.
authors.forename: Isabelle
authors.initials: I
authors.lastname: Sanyas
authors.affiliation: University of Lyon, University of Lyon1, CGΦMC, UMR CNRS 5534, F-69100 Villeurbanne, France.
authors.forename: Muriel
authors.initials: M
authors.lastname: Bozon
authors.affiliation: University of Lyon, University of Lyon1, CGΦMC, UMR CNRS 5534, F-69100 Villeurbanne, France.
authors.forename: Karine
authors.initials: K
authors.lastname: Kindbeiter
authors.affiliation: CNRS UMR 7592, Institut Jacques Monod, University Paris Diderot, Sorbonne Paris Cité, F-75205 Paris, France.
authors.forename: Frédéric
authors.initials: F
authors.lastname: Causeret
authors.affiliation: CNRS UMR 7592, Institut Jacques Monod, University Paris Diderot, Sorbonne Paris Cité, F-75205 Paris, France.
authors.forename: Alessandra
authors.initials: A
authors.lastname: Pierani
authors.affiliation: University of Lyon, University of Lyon1, CGΦMC, UMR CNRS 5534, F-69100 Villeurbanne, France.
authors.forename: Julien
authors.initials: J
authors.lastname: Falk
authors.affiliation: University of Lyon, University of Lyon1, CGΦMC, UMR CNRS 5534, F-69100 Villeurbanne, France.
authors.forename: Frédéric
authors.initials: F
authors.lastname: Moret
authors.affiliation: University of Lyon, University of Lyon1, CGΦMC, UMR CNRS 5534, F-69100 Villeurbanne, France.
authors.forename: Valérie
authors.initials: V
authors.lastname: Castellani
mesh_terms: D000818:Animals; D015153:Blotting, Western; D002455:Cell Division / Q000502:physiology*; D016764:Cell Polarity / Q000502:physiology*; D005455:Fluorescent Antibody Technique; D006367:HeLa Cells; D006801:Humans; D017403:In Situ Hybridization; D036341:Intercellular Signaling Peptides and Proteins / Q000378:metabolism; D051379:Mice; D018345:Mice, Knockout; D009419:Nerve Tissue Proteins / Q000378:metabolism; D046569:Neuroepithelial Cells / Q000502:physiology*; D039921:Neuropilins / Q000378:metabolism; D039961:Semaphorins / Q000134:cerebrospinal fluid* / Q000378:metabolism*; D013116:Spinal Cord / Q000166:cytology / Q000196:embryology*; D018709:Statistics, Nonparametric
chemical_list: D036341:Intercellular Signaling Peptides and Proteins; D009419:Nerve Tissue Proteins; D039921:Neuropilins; D039961:Semaphorins; C095114:collapsin response mediator protein-2