ADAM13 induces cranial neural crest by cleaving class B Ephrins and regulating Wnt signaling.
The cranial neural crest (CNC) consists of multipotent embryonic cells that contribute to craniofacial structures and other cells and tissues of the vertebrate head. During embryogenesis, CNC is induced at the neural plate boundary through the interplay of several major signaling pathways. Here, we report that the metalloproteinase activity of ADAM13 is required for early induction of CNC in Xenopus. In both cultured cells and X. tropicalis embryos, membrane-bound Ephrins (Efns) B1 and B2 were identified as substrates for ADAM13. ADAM13 upregulates canonical Wnt signaling and early expression of the transcription factor snail2, whereas EfnB1 inhibits the canonical Wnt pathway and snail2 expression. We propose that by cleaving class B Efns, ADAM13 promotes canonical Wnt signaling and early CNC induction.
Wei
Shuo
S
Department of Cell Biology and the Morphogenesis and Regenerative Medicine Institute, University of Virginia, Charlottesville, 22908, USA. sw9hy@virginia.edu
Xu
Guofeng
G
Bridges
Lance C
LC
Williams
Phoebe
P
White
Judith M
JM
DeSimone
Douglas W
DW
D051722:ADAM Proteins / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D019521:Body Patterning / Q000502:physiology; D002460:Cell Line; D004625:Embryo, Nonmammalian / Q000033:anatomy & histology / Q000502:physiology; D004627:Embryonic Induction; D036342:Ephrins / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism*; D009432:Neural Crest / Q000196:embryology* / Q000502:physiology; D015398:Signal Transduction / Q000502:physiology*; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism; D051153:Wnt Proteins / Q000235:genetics / Q000378:metabolism*; D014981:Xenopus / Q000033:anatomy & histology / Q000196:embryology* / Q000378:metabolism; D029867:Xenopus Proteins / Q000235:genetics / Q000378:metabolism*
D036342:Ephrins; D008565:Membrane Proteins; D014157:Transcription Factors; D051153:Wnt Proteins; D029867:Xenopus Proteins; D051722:ADAM Proteins; C104937:ADAM33 protein, Xenopus