title: Gas2l3 is essential for brain morphogenesis and development.
abstract: Growth arrest-specific 2-like 3 (Gas2l3) is a newly discovered cell cycle protein and a cytoskeleton orchestrator that binds both actin filament and microtubule networks. Studies of cultured mammalian cells established Gas2l3 as a regulator of the cell division process, in particular cytokinesis and cell abscission. Thus far, the role of Gas2l3 in vivo remains entirely unknown. In order to investigate Gas2l3 in developing vertebrates, we cloned the zebrafish gene. Spatiotemporal analysis of gas2l3 expression revealed a ubiquitous maternal transcript as well as a zygotic transcript primarily restricted to brain tissues. We next conducted a series of loss-of-function experiments, and searched for developmental anomalies at the end of the segmentation period. Our analysis revealed abnormal brain morphogenesis and ventricle formation in gas2l3 knockdown embryos. This signature phenotype could be rescued by elevated levels of gas2l3 RNA. At the tissue level, gas2l3 downregulation interferes with cell proliferation, suggesting that the cell cycle activities of Gas2l3 are essential for brain tissue homeostasis. Altogether, this study provides the first insight into the function of gas2l3 in vivo, demonstrating its essential role in brain development.
authors.affiliation: The Mina and Everard Goodman Faculty of Life Sciences, Bar-Ilan University, Ramat-Gan 5290002, Israel; Advanced Materials and Nanotechnology Institute, Bar-Ilan University, Ramat-Gan 5290002, Israel.
authors.forename: Yaara
authors.initials: Y
authors.lastname: Sharaby
authors.affiliation: The Mina and Everard Goodman Faculty of Life Sciences, Bar-Ilan University, Ramat-Gan 5290002, Israel; Advanced Materials and Nanotechnology Institute, Bar-Ilan University, Ramat-Gan 5290002, Israel.
authors.forename: Roxane
authors.initials: R
authors.lastname: Lahmi
authors.affiliation: The Mina and Everard Goodman Faculty of Life Sciences, Bar-Ilan University, Ramat-Gan 5290002, Israel; Advanced Materials and Nanotechnology Institute, Bar-Ilan University, Ramat-Gan 5290002, Israel.
authors.forename: Omer
authors.initials: O
authors.lastname: Amar
authors.affiliation: The Mina and Everard Goodman Faculty of Life Sciences, Bar-Ilan University, Ramat-Gan 5290002, Israel; Leslie and Susan Gonda Multidisciplinary Brain Research Center, Bar-Ilan University, Ramat-Gan 5290002, Israel.
authors.forename: Idan
authors.initials: I
authors.lastname: Elbaz
authors.affiliation: The Mina and Everard Goodman Faculty of Life Sciences, Bar-Ilan University, Ramat-Gan 5290002, Israel; Leslie and Susan Gonda Multidisciplinary Brain Research Center, Bar-Ilan University, Ramat-Gan 5290002, Israel.
authors.forename: Tali
authors.initials: T
authors.lastname: Lerer-Goldshtein
authors.affiliation: Faculty of Engineering, Bar-Ilan University, Ramat-Gan 5290002, Israel.
authors.forename: Aryeh M
authors.initials: AM
authors.lastname: Weiss
authors.affiliation: The Mina and Everard Goodman Faculty of Life Sciences, Bar-Ilan University, Ramat-Gan 5290002, Israel; Leslie and Susan Gonda Multidisciplinary Brain Research Center, Bar-Ilan University, Ramat-Gan 5290002, Israel.
authors.forename: Lior
authors.initials: L
authors.lastname: Appelbaum
authors.affiliation: The Mina and Everard Goodman Faculty of Life Sciences, Bar-Ilan University, Ramat-Gan 5290002, Israel; Advanced Materials and Nanotechnology Institute, Bar-Ilan University, Ramat-Gan 5290002, Israel. Electronic address: amit.tzur@biu.ac.il.
authors.forename: Amit
authors.initials: A
authors.lastname: Tzur
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D001921:Brain / Q000196:embryology*; D018797:Cell Cycle Proteins / Q000235:genetics / Q000378:metabolism*; D003598:Cytoskeletal Proteins / Q000235:genetics / Q000378:metabolism*; D017931:DNA Primers / Q000235:genetics; D055785:Gene Knockdown Techniques; D006367:HeLa Cells; D006801:Humans; D017403:In Situ Hybridization; D020287:In Situ Nick-End Labeling; D008840:Microfilament Proteins / Q000378:metabolism*; D008856:Microscopy, Fluorescence; D008869:Microtubule-Associated Proteins / Q000378:metabolism*; D008969:Molecular Sequence Data; D009024:Morphogenesis / Q000235:genetics / Q000502:physiology*; D016415:Sequence Alignment; D017422:Sequence Analysis, DNA; D013045:Species Specificity; D015027:Zebrafish / Q000196:embryology* / Q000235:genetics*; D029961:Zebrafish Proteins / Q000235:genetics / Q000378:metabolism*
chemical_list: D018797:Cell Cycle Proteins; D003598:Cytoskeletal Proteins; D017931:DNA Primers; C000593002:Gas2l3 protein, zebrafish; D008840:Microfilament Proteins; D008869:Microtubule-Associated Proteins; D029961:Zebrafish Proteins
keywords: Brain morphogenesis; Cell proliferation; Cytoskeleton; Spectraplakin