title: Cdon promotes neural crest migration by regulating N-cadherin localization.
abstract: Neural crest cells (NCCs) are essential embryonic progenitor cells that are unique to vertebrates and form a remarkably complex and coordinated system of highly motile cells. Migration of NCCs occurs along specific pathways within the embryo in response to both environmental cues and cell-cell interactions within the neural crest population. Here, we demonstrate a novel role for the putative Sonic hedgehog (Shh) receptor and cell adhesion regulator, cdon, in zebrafish neural crest migration. cdon is expressed in developing premigratory NCCs but is downregulated once the cells become migratory. Knockdown of cdon results in aberrant migration of trunk NCCs: crestin positive cells can emigrate out of the neural tube but stall shortly after the initiation of migration. Live cell imaging analysis demonstrates reduced directedness of migration, increased velocity and mispositioned cell protrusions. In addition, transplantation analysis suggests that cdon is required cell-autonomously for directed NCC migration in the trunk. Interestingly, N-cadherin is mislocalized following cdon knockdown suggesting that the role of cdon in NCCs is to regulate N-cadherin localization. Our results reveal a novel role for cdon in zebrafish neural crest migration, and suggest a mechanism by which Cdon is required to localize N-cadherin to the cell membrane in migratory NCCs for directed migration.
authors.affiliation: Department of Craniofacial Biology, School of Dental Medicine, Anschutz Medical Campus, University of Colorado, Aurora, CO 80045, USA; Cell Biology, Stem Cells, and Development Graduate Program, Anschutz Medical Campus, University of Colorado, Aurora, CO 80045, USA.
authors.forename: Davalyn R
authors.initials: DR
authors.lastname: Powell
authors.affiliation: Department of Craniofacial Biology, School of Dental Medicine, Anschutz Medical Campus, University of Colorado, Aurora, CO 80045, USA; Cell Biology, Stem Cells, and Development Graduate Program, Anschutz Medical Campus, University of Colorado, Aurora, CO 80045, USA.
authors.forename: Jason S
authors.initials: JS
authors.lastname: Williams
authors.affiliation: Department of Craniofacial Biology, School of Dental Medicine, Anschutz Medical Campus, University of Colorado, Aurora, CO 80045, USA.
authors.forename: Laura
authors.initials: L
authors.lastname: Hernandez-Lagunas
authors.affiliation: Department of Cell and Developmental biology, School of Medicine and USA Rocky Mountain Taste and Smell Center, Anschutz Medical Campus , University of Colorado, Aurora, CO 80045, USA.
authors.forename: Ernesto
authors.initials: E
authors.lastname: Salcedo
authors.affiliation: Department of Pharmacology, School of Medicine, Anschutz Medical Campus, University of Colorado, Aurora, CO 80045, USA.
authors.forename: Jenean H
authors.initials: JH
authors.lastname: O'Brien
authors.affiliation: Department of Craniofacial Biology, School of Dental Medicine, Anschutz Medical Campus, University of Colorado, Aurora, CO 80045, USA. Electronic address: Kristin.Artinger@ucdenver.edu.
authors.forename: Kristin Bruk
authors.initials: KB
authors.lastname: Artinger
mesh_terms: D000818:Animals; D015820:Cadherins / Q000378:metabolism*; D015815:Cell Adhesion Molecules / Q000235:genetics / Q000378:metabolism*; D002465:Cell Movement; D022081:Cell Surface Extensions / Q000378:metabolism; D004625:Embryo, Nonmammalian / Q000378:metabolism; D055785:Gene Knockdown Techniques; D053823:Hedgehog Proteins / Q000378:metabolism; D009432:Neural Crest / Q000166:cytology* / Q000378:metabolism*; D021381:Protein Transport; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction; D060726:Torso / Q000196:embryology; D015027:Zebrafish / Q000378:metabolism*; D029961:Zebrafish Proteins / Q000235:genetics / Q000378:metabolism*
chemical_list: D015820:Cadherins; C000605819:Cdh2 protein, zebrafish; C000602626:Cdon protein, zebrafish; D015815:Cell Adhesion Molecules; D053823:Hedgehog Proteins; D012333:RNA, Messenger; C524053:Shha protein, zebrafish; D029961:Zebrafish Proteins
keywords: Adhesion; Cell migration; Neural crest; Shh signaling; Zebrafish