The early dorsal signal in vertebrate embryos requires endolysosomal membrane trafficking

Fertilization triggers cytoplasmic movements in the frog egg that lead in mysterious ways to the stabilization of beta-catenin on the dorsal side of the embryo. The novel Huluwa (Hwa) transmembrane protein, identified in China, is translated specifically in the dorsal side, acting as an egg cytoplasmic determinant essential for beta-catenin stabilization. The Wnt signaling pathway requires macropinocytosis and the sequestration inside multivesicular bodies (MVBs, the precursors of endolysosomes) of Axin1 and Glycogen Synthase Kinase 3 (GSK3) that normally destroy beta-catenin. In Xenopus, the Wnt-like activity of GSK3 inhibitors and of Hwa mRNA can be blocked by brief treatment with inhibitors of membrane trafficking or lysosomes at the 32-cell stage. In dorsal blastomeres, lysosomal cathepsin is activated and intriguing MVBs surrounded by electron dense vesicles are formed at the 64-cell stage. We conclude that membrane trafficking and lysosomal activity are critically important for the earliest asymmetries in vertebrate embryonic development. Dorsal axis development in Xenopus requires an early Wnt-like signal that stabilizes beta-catenin. We review experiments showing that a membrane protein called Huluwa and lysosomes are more active on the dorsal side. The graphical abstract shows multivesicular bodies enriched specifically in at the dorsal side of the 64-cell embryo.image

Automated summary

Fertilization triggers cytoplasmic movements that stabilize beta-catenin on the dorsal side of the frog embryo. The Hwa protein, translated specifically on the dorsal side, acts as a crucial determinant for beta-catenin stabilization. Membrane trafficking and lysosomal activity play critical roles in the early asymmetries of vertebrate embryonic development.