title: Loss of Xenopus cadherin-11 leads to increased Wnt/β-catenin signaling and up-regulation of target genes c-myc and cyclin D1 in neural crest.
abstract: Xenopus cadherin-11 (Xcadherin-11) is an exceptional cadherin family member, which is predominantly expressed in cranial neural crest cells (NCCs). Apart from mediating cell-cell adhesion it promotes cranial NCC migration by initiating filopodia and lamellipodia formation. Here, we demonstrate an unexpected function of Xcadherin-11 in NCC specification by interfering with canonical Wnt/β-catenin signaling. Loss-of-function experiments, using a specific antisense morpholino oligonucleotide against Xcadherin-11, display a nuclear β-catenin localization in cranial NCCs and a broader expression domain of the proto-oncogene cyclin D1 which proceeds c-myc up-regulation. Additionally, we observe an enhanced NCC proliferation and an expansion of specific NCC genes like AP2 and Sox10. Thereby, we could allocate NCC proliferation and specification to different gene functions. To clarify which domain in Xcadherin-11 is required for early NCC development we tested different deletion mutants for their rescue ability in Xcadherin-11 morphants. We identified the cytoplasmic tail, specifically the β-catenin binding domain, to be necessary for proper NCC development. We propose that Xcadherin-11 is necessary for controlled NCC proliferation and early NCC specification in tuning the expression of the canonical Wnt/β-catenin target genes cyclin D1 and c-myc by regulating the concentration of the nuclear pool of β-catenin.
authors: KIT, Campus South, Zoological Institute, Department of Cell and Developmental Biology, 76131 Karlsruhe, Germany.
authors: Almut
authors: A
authors: Koehler
authors: Judith
authors: J
authors: Schlupf
authors: Martina
authors: M
authors: Schneider
authors: Bianca
authors: B
authors: Kraft
authors: Claudia
authors: C
authors: Winter
authors: Jubin
authors: J
authors: Kashef
mesh_terms: D021581:Active Transport, Cell Nucleus / Q000502:physiology; D000818:Animals; D015820:Cadherins / Q000172:deficiency* / Q000235:genetics; D002465:Cell Movement / Q000502:physiology; D049109:Cell Proliferation; D019938:Cyclin D1 / Q000378:metabolism; D018507:Gene Expression Regulation, Developmental / Q000235:genetics / Q000502:physiology*; D007150:Immunohistochemistry; D008156:Luciferases; D009432:Neural Crest / Q000166:cytology* / Q000196:embryology / Q000378:metabolism*; D016271:Proto-Oncogene Proteins c-myc / Q000378:metabolism; D060888:Real-Time Polymerase Chain Reaction; D060449:Wnt Signaling Pathway / Q000235:genetics / Q000502:physiology*; D014982:Xenopus laevis / Q000196:embryology*; D051176:beta Catenin / Q000378:metabolism*
chemical_list: D015820:Cadherins; D016271:Proto-Oncogene Proteins c-myc; D051176:beta Catenin; D019938:Cyclin D1; C086960:osteoblast cadherin; D008156:Luciferases
keywords: C-myc; Cadherin-11; Cadherins; Cyclin D1; Neural crest; Proliferation; β-catenin