title: Caldesmon regulates actin dynamics to influence cranial neural crest migration in Xenopus.
abstract: Caldesmon (CaD) is an important actin modulator that associates with actin filaments to regulate cell morphology and motility. Although extensively studied in cultured cells, there is little functional information regarding the role of CaD in migrating cells in vivo. Here we show that nonmuscle CaD is highly expressed in both premigratory and migrating cranial neural crest cells of Xenopus embryos. Depletion of CaD with antisense morpholino oligonucleotides causes cranial neural crest cells to migrate a significantly shorter distance, prevents their segregation into distinct migratory streams, and later results in severe defects in cartilage formation. Demonstrating specificity, these effects are rescued by adding back exogenous CaD. Interestingly, CaD proteins with mutations in the Ca(2+)-calmodulin-binding sites or ErK/Cdk1 phosphorylation sites fail to rescue the knockdown phenotypes, whereas mutation of the PAK phosphorylation site is able to rescue them. Analysis of neural crest explants reveals that CaD is required for the dynamic arrangements of actin and, thus, for cell shape changes and process formation. Taken together, these results suggest that the actin-modulating activity of CaD may underlie its critical function and is regulated by distinct signaling pathways during normal neural crest migration.
authors.affiliation: Division of Biology, California Institute of Technology, Pasadena, CA 91125, USA.
authors.forename: Shuyi
authors.initials: S
authors.lastname: Nie
authors.forename: Yun
authors.initials: Y
authors.lastname: Kee
authors.forename: Marianne
authors.initials: M
authors.lastname: Bronner-Fraser
mesh_terms: D008841:Actin Cytoskeleton / Q000378:metabolism; D000199:Actins / Q000378:metabolism*; D000595:Amino Acid Sequence; D000818:Animals; D002148:Calmodulin-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D002356:Cartilage / Q000254:growth & development / Q000378:metabolism; D002465:Cell Movement; D002478:Cells, Cultured; D055785:Gene Knockdown Techniques; D007814:Larva / Q000033:anatomy & histology / Q000254:growth & development / Q000378:metabolism; D008969:Molecular Sequence Data; D060172:Morpholinos / Q000235:genetics; D009432:Neural Crest / Q000166:cytology / Q000254:growth & development* / Q000378:metabolism; D010590:Phalloidine / Q000378:metabolism; D016415:Sequence Alignment; D015398:Signal Transduction; D012886:Skull / Q000254:growth & development* / Q000378:metabolism; D014982:Xenopus laevis / Q000033:anatomy & histology / Q000254:growth & development* / Q000378:metabolism
chemical_list: D000199:Actins; D002148:Calmodulin-Binding Proteins; D060172:Morpholinos; D010590:Phalloidine