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Development January 1, 2018; 145 (7):

Head formation requires Dishevelled degradation that is mediated by March2 in concert with Dapper1.

Lee H , Cheong SM , Han W , Koo Y , Jo SB , Cho GS , Yang JS , Kim S , Han JK .

Dishevelled (Dvl/Dsh) is a key scaffold protein that propagates Wnt signaling essential for embryogenesis and homeostasis. However, whether the antagonism of Wnt signaling that is necessary for vertebrate head formation can be achieved through regulation of Dsh protein stability is unclear. Here, we show that membrane-associated RING-CH2 (March2), a RING-type E3 ubiquitin ligase, antagonizes Wnt signaling by regulating the turnover of Dsh protein via ubiquitin-mediated lysosomal degradation in the prospective head region of Xenopus We further found that March2 acquires regional and functional specificities for head formation from the Dsh-interacting protein Dapper1 (Dpr1). Dpr1 stabilizes the interaction between March2 and Dsh in order to mediate ubiquitylation and the subsequent degradation of Dsh protein only in the dorso-animal region of Xenopus embryo. These results suggest that March2 restricts cytosolic pools of Dsh protein and reduces the need for Wnt signaling in precise vertebrate head development.

PubMed ID: 29549110
Article link: Development

Species referenced: Xenopus
Genes referenced: chrd.1 ctnnb1 dact1 dvl1 dvl2 eea1 egr2 en2 foxg1 gsc lamp1 lrp6 marchf2 myc nodal nodal1 nodal3.1 nodal3.2 not odc1 otx2 rab7a sox2 tbxt wnt8a
GO keywords: Wnt signaling pathway [+]
Morpholinos: dact1 MO3 dvl2 MO1 marchf2 MO1 marchf2 MO2 marchf2 MO3

Article Images: [+] show captions