title: FoxD3 regulates cranial neural crest EMT via downregulation of tetraspanin18 independent of its functions during neural crest formation.
abstract: The scaffolding protein tetraspanin18 (Tspan18) maintains epithelial cadherin-6B (Cad6B) to antagonize chick cranial neural crest epithelial-to-mesenchymal transition (EMT). For migration to take place, Tspan18 must be downregulated. Here, we characterize the role of the winged-helix transcription factor FoxD3 in the control of Tspan18 expression. Although we previously found that Tspan18 mRNA persists several hours past the stage it would normally be downregulated in FoxD3-deficient neural folds, we now show that Tspan18 expression eventually declines. This indicates that while FoxD3 is crucial for initial downregulation of Tspan18, other factors subsequently impact Tspan18 expression. Remarkably, the classical EMT transcription factor Snail2 is not one of these factors. As in other vertebrates, FoxD3 is required for chick cranial neural crest specification and migration, however, FoxD3 has surprisingly little impact on chick cranial neural crest cell survival. Strikingly, Tspan18 knockdown rescues FoxD3-dependent neural crest migration defects, although neural crest specification is still deficient. This indicates that FoxD3 promotes cranial neural crest EMT by eliciting Tspan18 downregulation separable from its Tspan18-independent activity during neural crest specification and survival.
authors.affiliation: Department of Genetics, Cell Biology, and Development, 6-160 Jackson Hall, 321 Church St. SE, University of Minnesota, Minneapolis, MN 55455, USA.
authors.forename: Corinne L
authors.initials: CL
authors.lastname: Fairchild
authors.affiliation: Department of Genetics, Cell Biology, and Development, 6-160 Jackson Hall, 321 Church St. SE, University of Minnesota, Minneapolis, MN 55455, USA.
authors.forename: Joseph P
authors.initials: JP
authors.lastname: Conway
authors.affiliation: Department of Animal and Avian Sciences, 1405 Animal Sciences Center, University of Maryland, College Park, MD 20742, USA.
authors.forename: Andrew T
authors.initials: AT
authors.lastname: Schiffmacher
authors.affiliation: Department of Animal and Avian Sciences, 1405 Animal Sciences Center, University of Maryland, College Park, MD 20742, USA.
authors.forename: Lisa A
authors.initials: LA
authors.lastname: Taneyhill
authors.affiliation: Department of Genetics, Cell Biology, and Development, 6-160 Jackson Hall, 321 Church St. SE, University of Minnesota, Minneapolis, MN 55455, USA. Electronic address: gammi001@umn.edu.
authors.forename: Laura S
authors.initials: LS
authors.lastname: Gammill
mesh_terms: D000818:Animals; D030161:Avian Proteins / Q000235:genetics / Q000378:metabolism; D002465:Cell Movement / Q000235:genetics; D002470:Cell Survival / Q000235:genetics; D002642:Chick Embryo; D015536:Down-Regulation / Q000235:genetics*; D058750:Epithelial-Mesenchymal Transition / Q000235:genetics*; D051858:Forkhead Transcription Factors / Q000235:genetics* / Q000378:metabolism*; D018507:Gene Expression Regulation, Developmental; D009432:Neural Crest / Q000378:metabolism*; D059470:Tetraspanins / Q000235:genetics* / Q000378:metabolism*; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism
chemical_list: D030161:Avian Proteins; D051858:Forkhead Transcription Factors; D059470:Tetraspanins; D014157:Transcription Factors
keywords: EMT; FoxD3; Migration; Neural crest; Tetraspanin