title: Dachsous1b cadherin regulates actin and microtubule cytoskeleton during early zebrafish embryogenesis.
abstract: Dachsous (Dchs), an atypical cadherin, is an evolutionarily conserved regulator of planar cell polarity, tissue size and cell adhesion. In humans, DCHS1 mutations cause pleiotropic Van Maldergem syndrome. Here, we report that mutations in zebrafish dchs1b and dchs2 disrupt several aspects of embryogenesis, including gastrulation. Unexpectedly, maternal zygotic (MZ) dchs1b mutants show defects in the earliest developmental stage, egg activation, including abnormal cortical granule exocytosis (CGE), cytoplasmic segregation, cleavages and maternal mRNA translocation, in transcriptionally quiescent embryos. Later, MZdchs1b mutants exhibit altered dorsal organizer and mesendodermal gene expression, due to impaired dorsal determinant transport and Nodal signaling. Mechanistically, MZdchs1b phenotypes can be explained in part by defective actin or microtubule networks, which appear bundled in mutants. Accordingly, disruption of actin cytoskeleton in wild-type embryos phenocopied MZdchs1b mutant defects in cytoplasmic segregation and CGE, whereas interfering with microtubules in wild-type embryos impaired dorsal organizer and mesodermal gene expression without perceptible earlier phenotypes. Moreover, the bundled microtubule phenotype was partially rescued by expressing either full-length Dchs1b or its intracellular domain, suggesting that Dchs1b affects microtubules and some developmental processes independent of its known ligand Fat. Our results indicate novel roles for vertebrate Dchs in actin and microtubule cytoskeleton regulation in the unanticipated context of the single-celled embryo.
authors.affiliation: Department of Developmental Biology, Washington University School of Medicine in St. Louis, St. Louis, MO 63110, USA.
authors.forename: Nanbing
authors.initials: N
authors.lastname: Li-Villarreal
authors.affiliation: Department of Developmental and Molecular Biology, Albert Einstein College of Medicine, Yeshiva University, Bronx, NY 10461, USA.
authors.forename: Meredyth M
authors.initials: MM
authors.lastname: Forbes
authors.affiliation: Department of Internal Medicine, Washington University School of Medicine in St. Louis, St. Louis, MO 63110, USA.
authors.forename: Andrew J
authors.initials: AJ
authors.lastname: Loza
authors.affiliation: Department of Developmental Biology, Washington University School of Medicine in St. Louis, St. Louis, MO 63110, USA.
authors.forename: Jiakun
authors.initials: J
authors.lastname: Chen
authors.affiliation: Division of Basic Sciences, Fred Hutchinson Cancer Research Center, Seattle,  WA 98109, USA.
authors.forename: Taylur
authors.initials: T
authors.lastname: Ma
authors.affiliation: Division of Basic Sciences, Fred Hutchinson Cancer Research Center, Seattle,  WA 98109, USA.
authors.forename: Kathryn
authors.initials: K
authors.lastname: Helde
authors.affiliation: Division of Basic Sciences, Fred Hutchinson Cancer Research Center, Seattle,  WA 98109, USA.
authors.forename: Cecilia B
authors.initials: CB
authors.lastname: Moens
authors.affiliation: Department of Developmental Biology, Washington University School of Medicine in St. Louis, St. Louis, MO 63110, USA.
authors.forename: Jimann
authors.initials: J
authors.lastname: Shin
authors.affiliation: Department of Developmental Biology, Washington University School of Medicine in St. Louis, St. Louis, MO 63110, USA.
authors.forename: Atsushi
authors.initials: A
authors.lastname: Sawada
authors.affiliation: Department of Developmental Biology, Washington University School of Medicine in St. Louis, St. Louis, MO 63110, USA.
authors.forename: Anna E
authors.initials: AE
authors.lastname: Hindes
authors.affiliation: Department of Molecular and Cellular Biology, Harvard University, Cambridge, MA 02138, USA.
authors.forename: Julien
authors.initials: J
authors.lastname: Dubrulle
authors.affiliation: Department of Molecular and Cellular Biology, Harvard University, Cambridge, MA 02138, USA.
authors.forename: Alexander F
authors.initials: AF
authors.lastname: Schier
authors.affiliation: Department of Internal Medicine, Washington University School of Medicine in St. Louis, St. Louis, MO 63110, USA.
authors.forename: Gregory D
authors.initials: GD
authors.lastname: Longmore
authors.affiliation: Department of Developmental and Molecular Biology, Albert Einstein College of Medicine, Yeshiva University, Bronx, NY 10461, USA Department of Neuroscience, Albert Einstein College of Medicine, Yeshiva University, Bronx, NY 10461, USA.
authors.forename: Florence L
authors.initials: FL
authors.lastname: Marlow
authors.affiliation: Department of Developmental Biology, Washington University School of Medicine in St. Louis, St. Louis, MO 63110, USA solnical@wustl.edu.
authors.forename: Lilianna
authors.initials: L
authors.lastname: Solnica-Krezel
mesh_terms: D000199:Actins / Q000378:metabolism*; D000818:Animals; D015820:Cadherins / Q000235:genetics / Q000378:metabolism*; D003599:Cytoskeleton / Q000502:physiology*; D017931:DNA Primers / Q000235:genetics; D005089:Exocytosis / Q000502:physiology; D005260:Female; D007150:Immunohistochemistry; D017403:In Situ Hybridization; D018613:Microscopy, Confocal; D008870:Microtubules / Q000378:metabolism*; D061848:Optical Imaging; D010053:Ovary / Q000033:anatomy & histology; D012333:RNA, Messenger / Q000378:metabolism; D060888:Real-Time Polymerase Chain Reaction; D015027:Zebrafish / Q000196:embryology*; D029961:Zebrafish Proteins / Q000235:genetics / Q000378:metabolism*
chemical_list: D000199:Actins; D015820:Cadherins; C000601556:DCHS1b protein, zebrafish; D017931:DNA Primers; D012333:RNA, Messenger; D029961:Zebrafish Proteins
keywords: Actin; Cell fate; Egg activation; Microtubule; Morphogenesis; dchs1b