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Sci Rep January 1, 2019; 9 (1): 15645.

Lef1 regulates caveolin expression and caveolin dependent endocytosis, a process necessary for Wnt5a/Ror2 signaling during Xenopus gastrulation.

Puzik K , Tonnier V , Opper I , Eckert A , Zhou L , Kratzer MC , Noble FL , Nienhaus GU , Gradl D .

The activation of distinct branches of the Wnt signaling network is essential for regulating early vertebrate development. Activation of the canonical Wnt/β-catenin pathway stimulates expression of β-catenin-Lef/Tcf regulated Wnt target genes and a regulatory network giving rise to the formation of the Spemann organizer. Non-canonical pathways, by contrast, mainly regulate cell polarization and migration, in particular convergent extension movements of the trunk mesoderm during gastrulation. By transcriptome analyses, we found caveolin1, caveolin3 and cavin1 to be regulated by Lef1 in the involuting mesoderm of Xenopus embryos at gastrula stages. We show that caveolins and caveolin dependent endocytosis are necessary for proper gastrulation, most likely by interfering with Wnt5a/Ror2 signaling. Wnt5a regulates the subcellular localization of receptor complexes, including Ror2 homodimers, Ror2/Fzd7 and Ror2/dsh heterodimers in an endocytosis dependent manner. Live-cell imaging revealed endocytosis of Ror2/caveolin1 complexes. In Xenopus explants, in the presence of Wnt5a, these receptor clusters remain stable exclusively at the basolateral side, suggesting that endocytosis of non-canonical Wnt/receptor complexes preferentially takes place at the apical membrane. In support of this blocking endocytosis with inhibitors prevents the effects of Wnt5a. Thus, target genes of Lef1 interfere with Wnt5a/Ror2 signaling to coordinate gastrulation movements.

PubMed ID: 31666627
PMC ID: PMC6821757
Article link: Sci Rep
Grant support: [+]
Genes referenced: cav1 cav3.1 chrd.1 cltc fzd7 lef1 pbk pcdh8.2 ror2 wnt5a
GO keywords: gastrulation [+]
Morpholinos: Cav3MO cav1MO cavin1MO

Article Images: [+] show captions
References [+] :
Behrens, Functional interaction of beta-catenin with the transcription factor LEF-1. 1996, Pubmed, Xenbase

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