title: MRCK-1 Drives Apical Constriction in C. elegans by Linking Developmental Patterning to Force Generation.
abstract: Apical constriction is a change in cell shape that drives key morphogenetic events including gastrulation and neural tube formation. Apical force-producing actomyosin networks drive apical constriction by contracting while connected to cell-cell junctions. The mechanisms by which developmental patterning regulates these actomyosin networks and associated junctions with spatial precision are not fully understood. Here we identify a myosin light-chain kinase MRCK-1 as a key regulator of C. elegans gastrulation that integrates spatial and developmental patterning information. We show that MRCK-1 is required for activation of contractile actomyosin dynamics and elevated cortical tension in the apical cell cortex of endoderm precursor cells. MRCK-1 is apically localized by active Cdc42 at the external, cell-cell contact-free surfaces of apically constricting cells, downstream of cell fate determination mechanisms. We establish that the junctional components α-catenin, β-catenin, and cadherin become highly enriched at the apical junctions of apically constricting cells and that MRCK-1 and myosin activity are required in vivo for this enrichment. Taken together, our results define mechanisms that position a myosin activator to a specific cell surface where it both locally increases cortical tension and locally enriches junctional components to facilitate apical constriction. These results reveal crucial links that can tie spatial information to local force generation to drive morphogenesis.
authors.affiliation: Biology Department, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA; Department of Pharmacology, University of North Carolina School of Medicine, Chapel Hill, NC 27599, USA. Electronic address: dmarston@unc.edu.
authors.forename: Daniel J
authors.initials: DJ
authors.lastname: Marston
authors.affiliation: Biology Department, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA.
authors.forename: Christopher D
authors.initials: CD
authors.lastname: Higgins
authors.affiliation: Biology Department, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA.
authors.forename: Kimberly A
authors.initials: KA
authors.lastname: Peters
authors.affiliation: Department of Cell Biology and Physiology, University of North Carolina School of Medicine, Chapel Hill, NC 27599, USA.
authors.forename: Timothy D
authors.initials: TD
authors.lastname: Cupp
authors.affiliation: Biology Department, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA; Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA.
authors.forename: Daniel J
authors.initials: DJ
authors.lastname: Dickinson
authors.affiliation: Biology Department, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA; Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA.
authors.forename: Ariel M
authors.initials: AM
authors.lastname: Pani
authors.affiliation: Biology Department, Duke University, Durham, NC 27708, USA.
authors.forename: Regan P
authors.initials: RP
authors.lastname: Moore
authors.affiliation: Biology Department, Duke University, Durham, NC 27708, USA.
authors.forename: Amanda H
authors.initials: AH
authors.lastname: Cox
authors.affiliation: Biology Department, Duke University, Durham, NC 27708, USA.
authors.forename: Daniel P
authors.initials: DP
authors.lastname: Kiehart
authors.affiliation: Biology Department, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA; Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA.
authors.forename: Bob
authors.initials: B
authors.lastname: Goldstein
mesh_terms: D000205:Actomyosin / Q000378:metabolism; D000818:Animals; D001696:Biomechanical Phenomena; D017173:Caenorhabditis elegans / Q000196:embryology* / Q000235:genetics* / Q000378:metabolism; D029742:Caenorhabditis elegans Proteins / Q000235:genetics* / Q000378:metabolism; D002448:Cell Adhesion; D018797:Cell Cycle Proteins / Q000235:genetics* / Q000378:metabolism; D002465:Cell Movement; D019204:GTP-Binding Proteins / Q000235:genetics* / Q000378:metabolism; D054262:Gastrulation; D005786:Gene Expression Regulation; D007365:Intercellular Junctions / Q000378:metabolism; D009218:Myosins / Q000378:metabolism; D017346:Protein Serine-Threonine Kinases / Q000235:genetics* / Q000378:metabolism
chemical_list: D029742:Caenorhabditis elegans Proteins; D018797:Cell Cycle Proteins; C081779:cdc-42 protein, C elegans; D000205:Actomyosin; C000625697:MRCK-1 kinase, C elegans; D017346:Protein Serine-Threonine Kinases; D019204:GTP-Binding Proteins; D009218:Myosins