title: The cytoskeleton-associated protein SCHIP1 is involved in axon guidance, and is required for piriform cortex and anterior commissure development.
abstract: SCHIP1 is a cytoplasmic partner of cortical cytoskeleton ankyrins. The IQCJ-SCHIP1 isoform is a component of axon initial segments and nodes of Ranvier of mature axons in peripheral and central nervous systems, where it associates with membrane complexes comprising cell adhesion molecules. SCHIP1 is also expressed in the mouse developing central nervous system during embryonic stages of active axonogenesis. Here, we identify a new and early role for SCHIP1 during axon development and establishment of the anterior commissure (AC). The AC is composed of axons from the piriform cortex, the anterior olfactory nucleus and the amygdala. Schip1 mutant mice displayed early defects in AC development that might result from impaired axon growth and guidance. In addition, mutant mice presented a reduced thickness of the piriform cortex, which affected projection neurons in layers 2/3 and was likely to result from cell death rather than from impairment of neuron generation or migration. Piriform cortex neurons from E14.5 mutant embryos displayed axon initiation/outgrowth delay and guidance defects in vitro. The sensitivity of growth cones to semaphorin 3F and Eph receptor B2, two repulsive guidance cues crucial for AC development, was increased, providing a possible basis for certain fiber tract alterations. Thus, our results reveal new evidence for the involvement of cortical cytoskeleton-associated proteins in the regulation of axon development and their importance for the formation of neuronal circuits.
authors.affiliation: INSERM, UMR-S 839, Paris F-75005, France Sorbonne Universités, UPMC Univ Paris 06, Paris F-75005, France Institut du Fer à Moulin, Paris F-75005, France.
authors.forename: Esther
authors.initials: E
authors.lastname: Klingler
authors.affiliation: INSERM, UMR-S 839, Paris F-75005, France Sorbonne Universités, UPMC Univ Paris 06, Paris F-75005, France Institut du Fer à Moulin, Paris F-75005, France.
authors.forename: Pierre-Marie
authors.initials: PM
authors.lastname: Martin
authors.affiliation: INSERM, UMR-S 839, Paris F-75005, France Sorbonne Universités, UPMC Univ Paris 06, Paris F-75005, France Institut du Fer à Moulin, Paris F-75005, France.
authors.forename: Marta
authors.initials: M
authors.lastname: Garcia
authors.affiliation: Sorbonne Universités, UPMC Univ Paris 06, Paris F-75005, France Institut de la Vision, INSERM, UMR-S 968, Paris F-75012, France CNRS, UMR 7210, Paris F-75012, France.
authors.forename: Caroline
authors.initials: C
authors.lastname: Moreau-Fauvarque
authors.affiliation: Université Claude Bernard Lyon 1, CNRS, UMR 5534, CGphiMC, Lyon F-69622, France.
authors.forename: Julien
authors.initials: J
authors.lastname: Falk
authors.affiliation: House Research Institute, Center for Neural Tumor Research, Los Angeles, CA 90095-1624, USA.
authors.forename: Fabrice
authors.initials: F
authors.lastname: Chareyre
authors.affiliation: Department of Head and Neck Surgery, David Geffen School of Medicine, UCLA, Los Angeles, CA 90027, USA.
authors.forename: Marco
authors.initials: M
authors.lastname: Giovannini
authors.affiliation: Sorbonne Universités, UPMC Univ Paris 06, Paris F-75005, France Institut de la Vision, INSERM, UMR-S 968, Paris F-75012, France CNRS, UMR 7210, Paris F-75012, France.
authors.forename: Alain
authors.initials: A
authors.lastname: Chédotal
authors.affiliation: INSERM, UMR-S 839, Paris F-75005, France Sorbonne Universités, UPMC Univ Paris 06, Paris F-75005, France Institut du Fer à Moulin, Paris F-75005, France.
authors.forename: Jean-Antoine
authors.initials: JA
authors.lastname: Girault
authors.affiliation: INSERM, UMR-S 839, Paris F-75005, France Sorbonne Universités, UPMC Univ Paris 06, Paris F-75005, France Institut du Fer à Moulin, Paris F-75005, France laurence.goutebroze@inserm.fr.
authors.forename: Laurence
authors.initials: L
authors.lastname: Goutebroze
mesh_terms: D000818:Animals; D066240:Anterior Commissure, Brain / Q000196:embryology* / Q000378:metabolism*; D001369:Axons / Q000378:metabolism*; D002352:Carrier Proteins / Q000378:metabolism*; D016923:Cell Death; D003599:Cytoskeleton / Q000378:metabolism*; D004622:Embryo, Mammalian / Q000378:metabolism; D020439:Growth Cones / Q000378:metabolism; D051379:Mice; D008817:Mice, Mutant Strains; D009419:Nerve Tissue Proteins / Q000378:metabolism; D066195:Piriform Cortex / Q000196:embryology* / Q000378:metabolism*; D036183:Receptor, EphB2 / Q000378:metabolism
chemical_list: D002352:Carrier Proteins; D009419:Nerve Tissue Proteins; C000600131:SCHIP1 protein, mouse; D036183:Receptor, EphB2
keywords: Anterior commissure; Axon growth and guidance; EPHB2; Piriform cortex; SCHIP1; SEMA3F