title: Polarized Rac-dependent protrusions drive epithelial intercalation in the embryonic epidermis of C. elegans.
abstract: Cell intercalation is a fundamental, coordinated cell rearrangement process that shapes tissues throughout animal development. Studies of intercalation within epithelia have focused almost exclusively on the localized constriction of specific apical junctions. Another widely deployed yet poorly understood alternative mechanism of epithelial intercalation relies on basolateral protrusive activity. Using the dorsal embryonic epidermis of Caenorhabditis elegans, we have investigated this alternative mechanism using high-resolution live cell microscopy and genetic analysis. We find that as dorsal epidermal cells migrate past one another they produce F-actin-rich protrusions polarized at their extending (medial) edges. These protrusions are controlled by the C. elegans Rac and RhoG orthologs CED-10 and MIG-2, which function redundantly to polarize actin polymerization upstream of the WAVE complex and WASP, respectively. We also identify UNC-73, the C. elegans ortholog of Trio, as a guanine nucleotide exchange factor (GEF) upstream of both CED-10 and MIG-2. Further, we identify a novel polarizing cue, CRML-1, which is the ortholog of human capping Arp2/3 myosin I linker (CARMIL), that localizes to the nonprotrusive lateral edges of dorsal cells. CRML-1 genetically suppresses UNC-73 function and, indirectly, actin polymerization. This network identifies a novel, molecularly conserved cassette that regulates epithelial intercalation via basolateral protrusive activity.
authors.affiliation: Graduate Program in Genetics, University of Wisconsin-Madison, 1117 W. Johnson Street, Madison, WI 53706, USA.
authors.forename: Elise
authors.initials: E
authors.lastname: Walck-Shannon
authors.affiliation: Department of Pharmacology and Lineberger Comprehensive Cancer Center, University of North Carolina, 101 Manning Drive, Chapel Hill, NC 27514, USA Center for Translational Cancer Research, Institute of Biosciences and Technology and Department of Medical Physiology, Texas A&M Health Science Center, 2121 W. Holcombe Boulevard, Houston, TX 77030, USA.
authors.forename: David
authors.initials: D
authors.lastname: Reiner
authors.affiliation: Graduate Program in Genetics, University of Wisconsin-Madison, 1117 W. Johnson Street, Madison, WI 53706, USA Department of Zoology, University of Wisconsin-Madison, 1117 W. Johnson Street, Madison, WI 53706, USA jdhardin@wisc.edu.
authors.forename: Jeff
authors.initials: J
authors.lastname: Hardin
mesh_terms: D000199:Actins / Q000378:metabolism; D000818:Animals; D019521:Body Patterning; D017173:Caenorhabditis elegans / Q000196:embryology*; D029742:Caenorhabditis elegans Proteins / Q000378:metabolism / Q000502:physiology; D002465:Cell Movement; D004817:Epidermis / Q000196:embryology*; D004848:Epithelium / Q000196:embryology*; D018507:Gene Expression Regulation, Developmental; D049452:Green Fluorescent Proteins / Q000378:metabolism; D009419:Nerve Tissue Proteins / Q000502:physiology; D034622:RNA Interference; D020744:rac GTP-Binding Proteins / Q000378:metabolism
chemical_list: D000199:Actins; C407268:CED-10 protein, C elegans; D029742:Caenorhabditis elegans Proteins; D009419:Nerve Tissue Proteins; C111263:UNC-73 protein, C elegans; C541355:crml-1 protein, C elegans; D049452:Green Fluorescent Proteins; C442327:Mig-2 protein, C elegans; D020744:rac GTP-Binding Proteins
keywords: CARMIL; Cell intercalation; LRRC16A; Morphogenesis; Rac GTPase; Trio