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Development 2018 Apr 04;1457:. doi: 10.1242/dev.158154.
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Xenopus ADAM19 regulates Wnt signaling and neural crest specification by stabilizing ADAM13.

Li J , Perfetto M , Neuner R , Bahudhanapati H , Christian L , Mathavan K , Bridges LC , Alfandari D , Wei S .

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.

PubMed ID: 29540504
PMC ID: PMC5963864
Article link: Development
Grant support: [+]

Species referenced: Xenopus
Genes referenced: adam12 adam13 adam19 adam28.2 canx foxd3 msx1 myc npb pax3 pax6 rax snai2 sox9 zic1
GO keywords: eye development [+]
Antibodies: Adam13 Ab1 adam19 AB1 canx Ab1
Morpholinos: adam12 MO1 adam19 MO3 adam19 MO4

Article Images: [+] show captions
References [+] :
Abbruzzese, The Wnt receptor Frizzled-4 modulates ADAM13 metalloprotease activity. 2015, Pubmed, Xenbase