title: Laminin β1a controls distinct steps during the establishment of digestive organ laterality.
abstract: Visceral organs, including the liver and pancreas, adopt asymmetric positions to ensure proper function. Yet the molecular and cellular mechanisms controlling organ laterality are not well understood. We identified a mutation affecting zebrafish laminin β1a (lamb1a) that disrupts left-right asymmetry of the liver and pancreas. In these mutants, the liver spans the midline and the ventral pancreatic bud remains split into bilateral structures. We show that lamb1a regulates asymmetric left-right gene expression in the lateral plate mesoderm (LPM). In particular, lamb1a functions in Kupffer's vesicle (KV), a ciliated organ analogous to the mouse node, to control the length and function of the KV cilia. Later during gut-looping stages, dynamic expression of Lamb1a is required for the bilayered organization and asymmetric migration of the LPM. Loss of Lamb1a function also results in aberrant protrusion of LPM cells into the gut. Collectively, our results provide cellular and molecular mechanisms by which extracellular matrix proteins regulate left-right organ morphogenesis.
authors.affiliation: Department of Biochemistry and Biophysics, Programs in Developmental and Stem Cell Biology, Genetics and Human Genetics, Liver Center and Diabetes Center, Institute for Regeneration Medicine, University of California, San Francisco, CA 94158, USA. hochgreb@caltech.edu
authors.forename: Tatiana
authors.initials: T
authors.lastname: Hochgreb-Hägele
authors.forename: Chunyue
authors.initials: C
authors.lastname: Yin
authors.forename: Daniel E S
authors.initials: DE
authors.lastname: Koo
authors.forename: Marianne E
authors.initials: ME
authors.lastname: Bronner
authors.forename: Didier Y R
authors.initials: DY
authors.lastname: Stainier
mesh_terms: D000818:Animals; D019521:Body Patterning / Q000235:genetics / Q000502:physiology; D002923:Cilia / Q000378:metabolism; D007839:Functional Laterality / Q000235:genetics / Q000502:physiology; D041981:Gastrointestinal Tract / Q000196:embryology / Q000378:metabolism; D018507:Gene Expression Regulation, Developmental / Q000235:genetics / Q000502:physiology; D007150:Immunohistochemistry; D017403:In Situ Hybridization; D007797:Laminin / Q000235:genetics / Q000378:metabolism*; D038081:Organogenesis / Q000235:genetics / Q000502:physiology; D015027:Zebrafish / Q000196:embryology* / Q000235:genetics / Q000378:metabolism*; D029961:Zebrafish Proteins / Q000235:genetics / Q000378:metabolism*
chemical_list: D007797:Laminin; D029961:Zebrafish Proteins; C462526:lamb1a protein, zebrafish
keywords: Asymmetry; Laminin; Organogenesis