title: CDC-42 Orients Cell Migration during Epithelial Intercalation in the Caenorhabditis elegans Epidermis.
abstract: Cell intercalation is a highly directed cell rearrangement that is essential for animal morphogenesis. As such, intercalation requires orchestration of cell polarity across the plane of the tissue. CDC-42 is a Rho family GTPase with key functions in cell polarity, yet its role during epithelial intercalation has not been established because its roles early in embryogenesis have historically made it difficult to study. To circumvent these early requirements, in this paper we use tissue-specific and conditional loss-of-function approaches to identify a role for CDC-42 during intercalation of the Caenorhabditis elegans dorsal embryonic epidermis. CDC-42 activity is enriched in the medial tips of intercalating cells, which extend as cells migrate past one another. Moreover, CDC-42 is involved in both the efficient formation and orientation of cell tips during cell rearrangement. Using conditional loss-of-function we also show that the PAR complex functions in tip formation and orientation. Additionally, we find that the sole C. elegans Eph receptor, VAB-1, functions during this process in an Ephrin-independent manner. Using epistasis analysis, we find that vab-1 lies in the same genetic pathway as cdc-42 and is responsible for polarizing CDC-42 activity to the medial tip. Together, these data establish a previously uncharacterized role for polarized CDC-42, in conjunction with PAR-6, PAR-3 and an Eph receptor, during epithelial intercalation.
authors.affiliation: Department of Zoology, University of Wisconsin-Madison, Madison, Wisconsin, United States of America.
authors.forename: Elise
authors.identifier: 0000-0001-5187-9965
authors.initials: E
authors.lastname: Walck-Shannon
authors.affiliation: Program in Genetics, University of Wisconsin-Madison, Madison, Wisconsin, United States of America.
authors.forename: Bethany
authors.initials: B
authors.lastname: Lucas
authors.affiliation: Department of Biology, Queen's University, Kingston, Ontario, Canada.
authors.forename: Ian
authors.initials: I
authors.lastname: Chin-Sang
authors.affiliation: Center for Translational Cancer Research, Institute of Biosciences and Technology and Department of Medical Physiology, Texas A&M Health Science Center, Houston, Texas, United States of America.
authors.forename: David
authors.initials: D
authors.lastname: Reiner
authors.affiliation: Department of Medicine, University of Wisconsin-Madison, Madison, Wisconsin, United States of America.
authors.forename: Kraig
authors.initials: K
authors.lastname: Kumfer
authors.affiliation: Department of Zoology, University of Wisconsin-Madison, Madison, Wisconsin, United States of America.
authors.forename: Hunter
authors.identifier: 0000-0001-9522-2797
authors.initials: H
authors.lastname: Cochran
authors.affiliation: Department of Zoology, University of Wisconsin-Madison, Madison, Wisconsin, United States of America.
authors.forename: William
authors.identifier: 0000-0002-7329-0286
authors.initials: W
authors.lastname: Bothfeld
authors.affiliation: Department of Zoology, University of Wisconsin-Madison, Madison, Wisconsin, United States of America.|Program in Genetics, University of Wisconsin-Madison, Madison, Wisconsin, United States of America.
authors.forename: Jeff
authors.identifier: 0000-0001-7399-6580
authors.initials: J
authors.lastname: Hardin
mesh_terms: D000818:Animals; D017173:Caenorhabditis elegans / Q000235:genetics* / Q000254:growth & development; D029742:Caenorhabditis elegans Proteins / Q000235:genetics*; D018797:Cell Cycle Proteins / Q000235:genetics*; D002465:Cell Movement / Q000235:genetics; D016764:Cell Polarity / Q000235:genetics; D047108:Embryonic Development / Q000235:genetics; D036342:Ephrins / Q000235:genetics; D004817:Epidermis / Q000254:growth & development / Q000378:metabolism; D004843:Epistasis, Genetic; D004848:Epithelium / Q000254:growth & development / Q000378:metabolism; D019204:GTP-Binding Proteins / Q000235:genetics*; D009024:Morphogenesis / Q000235:genetics; D009928:Organ Specificity; D017346:Protein Serine-Threonine Kinases / Q000235:genetics*; D020794:Receptor Protein-Tyrosine Kinases / Q000235:genetics*; D015398:Signal Transduction
chemical_list: D029742:Caenorhabditis elegans Proteins; D018797:Cell Cycle Proteins; D036342:Ephrins; C081779:cdc-42 protein, C elegans; C512642:par-6 protein, C elegans; D020794:Receptor Protein-Tyrosine Kinases; C111040:vab-1 protein, C elegans; C097238:PAR-3 protein, C elegans; D017346:Protein Serine-Threonine Kinases; D019204:GTP-Binding Proteins