Rab7 mediates Wnt-dependent mesoderm patterning and gastrulation in Xenopus

Abstract

Early embryogenesis requires tightly controlled temporal and spatial activity of growth factors. Modulation is achieved at multiple levels, from cellular transcription to tissue-scale propagation, concerning activation, maintenance, or termination of signaling. Intracellularly, the endolysosomal system emerged as important factor for such regulations. Endocytosis and early endosomes mainly orchestrate activation and transduction of signals, while late endosomes are thought to mediate lysosome-based termination. Only few reports attributed activating roles to late endosomes, mainly for Wnt pathway activation. In Xenopus, few is known about developmental roles of endosomal regulators, or their function for signaling, especially true for late endosomes. Therefore, we chose to analyze a hypothesized positive role of Rab7 in this context, a small GTPase mainly known for its role as a late endosomal regulator. We analyzed if Rab7 participates in early activation of growth factor signaling, focusing on Wnt signaling. We found rab7 expressed very localized throughout development, and inhibition resulted in strong gastrulation defects. Concomitantly, Rab7 was strictly required for both, exogenous activation and endogenous Wnt-mediated patterning of the mesoderm. Summary StatementThe late endosomal regulator Rab7 is required for gastrulation movements and axis elongation in Xenopus by positively regulating Wnt signaling-mediated mesoderm patterning.