Open AccessXenopus ADAM19 regulates Wnt signaling and neural crest specification by stabilizing ADAM13
Author(s) -
Jiejing Li,
Mark Perfetto,
Russell Neuner,
Harinath Bahudhanapati,
Laura Christian,
Ketan Mathavan,
Lance C. Bridges,
Dominique Alfandari,
Shuo Wei
Publication year - 2018
Publication title -
development
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.15
H-Index - 36
eISSN - 1477-9129
pISSN - 0950-1991
DOI - 10.1242/dev.158154
Subject(s) - wnt signaling pathway , gastrulation , xenopus , biology , neural crest , microbiology and biotechnology , neural plate , disintegrin , gene knockdown , ectopic expression , zebrafish , signal transduction , genetics , metalloproteinase , matrix metalloproteinase , embryogenesis , gene , embryo
During vertebrate gastrulation, canonical Wnt signaling induces the formation of neural plate border (NPB). Wnt is also thought to be required for the subsequent specification of neural crest (NC) lineage at the NPB, but the direct evidence is lacking. We found previously that the disintegrin metalloproteinase ADAM13 is required for Wnt activation and NC induction in Xenopus. Here we report that knockdown of ADAM13 or its close paralog ADAM19 severely downregulates Wnt activity at the NPB, inhibiting NC specification without affecting earlier NPB formation. Surprisingly, ADAM19 functions nonproteolytically in NC specification by interacting with ADAM13 and inhibiting its proteasomal degradation. Ectopic expression of stabilized ADAM13 mutants that function independently of ADAM19 can induce the NC marker/specifier snail2 in the future epidermis via Wnt signaling. These results unveil the essential roles of a novel protease-protease interaction in regulating a distinct wave of Wnt signaling, which directly specifies the NC lineage.