title: Sema6a and Plxna2 mediate spatially regulated repulsion within the developing eye to promote eye vesicle cohesion.
abstract: Organs are generated from collections of cells that coalesce and remain together as they undergo a series of choreographed movements to give the organ its final shape. We know little about the cellular and molecular mechanisms that regulate tissue cohesion during morphogenesis. Extensive cell movements underlie eye development, starting with the eye field separating to form bilateral vesicles that go on to evaginate from the forebrain. What keeps eye cells together as they undergo morphogenesis and extensive proliferation is unknown. Here, we show that plexina2 (Plxna2), a member of a receptor family best known for its roles in axon and cell guidance, is required alongside the repellent semaphorin 6a (Sema6a) to keep cells integrated within the zebrafish eye vesicle epithelium. sema6a is expressed throughout the eye vesicle, whereas plxna2 is restricted to the ventral vesicle. Knockdown of Plxna2 or Sema6a results in a loss of vesicle integrity, with time-lapse microscopy showing that eye progenitors either fail to enter the evaginating vesicles or delaminate from the eye epithelium. Explant experiments, and rescue of eye vesicle integrity with simultaneous knockdown of sema6a and plxna2, point to an eye-autonomous requirement for Sema6a/Plxna2. We propose a novel, tissue-autonomous mechanism of organ cohesion, with neutralization of repulsion suggested as a means to promote interactions between cells within a tissue domain.
authors.affiliation: Department of Cell Biology and Anatomy, Hotchkiss Brain Institute, Calgary, Alberta T2N 4N1, Canada.
authors.forename: Alicia M
authors.initials: AM
authors.lastname: Ebert
authors.affiliation: Department of Biochemistry and Molecular Biology, University of Calgary, Calgary, Alberta T2N 4N1, Canada.
authors.forename: Sarah J
authors.initials: SJ
authors.lastname: Childs
authors.affiliation: Department of Cell Biology and Anatomy, Hotchkiss Brain Institute, Calgary, Alberta T2N 4N1, Canada.
authors.forename: Carrie L
authors.initials: CL
authors.lastname: Hehr
authors.affiliation: Department of Cell Biology and Anatomy, Hotchkiss Brain Institute, Calgary, Alberta T2N 4N1, Canada.
authors.forename: Paula B
authors.initials: PB
authors.lastname: Cechmanek
authors.affiliation: Department of Cell Biology and Anatomy, Hotchkiss Brain Institute, Calgary, Alberta T2N 4N1, Canada smcfarla@ucalgary.ca.
authors.forename: Sarah
authors.initials: S
authors.lastname: McFarlane
mesh_terms: D000818:Animals; D001369:Axons / Q000378:metabolism; D002450:Cell Communication; D002465:Cell Movement; D049109:Cell Proliferation; D005123:Eye / Q000196:embryology*; D020869:Gene Expression Profiling; D018507:Gene Expression Regulation, Developmental; D049452:Green Fluorescent Proteins / Q000378:metabolism; D009024:Morphogenesis; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000502:physiology*; D016548:Prosencephalon / Q000196:embryology; D011956:Receptors, Cell Surface / Q000235:genetics / Q000502:physiology*; D039961:Semaphorins / Q000235:genetics / Q000502:physiology*; D015398:Signal Transduction; D013234:Stem Cells / Q000166:cytology; D015027:Zebrafish / Q000196:embryology / Q000235:genetics; D029961:Zebrafish Proteins / Q000235:genetics / Q000502:physiology*
chemical_list: D009419:Nerve Tissue Proteins; C000590394:Plxna2 protein, zebrafish; D011956:Receptors, Cell Surface; C000590393:Sema6a protein, zebrafish; D039961:Semaphorins; D029961:Zebrafish Proteins; D049452:Green Fluorescent Proteins
keywords: Morphogenesis; Plexin; Repulsion; Semaphorin; Zebrafish