bioRxiv Science⌕ Search

Biology subjects

Vick, P.

Publications and source records attributed to Vick, P..

3 recordsLinked to original sources

Rab7 mediates Wnt-dependent mesoderm patterning and gastrulation in Xenopus

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.

developmental biology↗

Bicc1 and dicer regulate left-right patterning through posttranscriptionalcontrol of the Nodal-inhibitor dand5

Rotating cilia at the vertebrate left-right organizer (LRO) generate an asymmetric leftward flow, which is sensed by cells at the left LRO margin. How the flow signal is processed and relayed to the laterality-determining Nodal cascade in the left lateral plate mesoderm (LPM) is largely unknown. We previously showed that flow down-regulates mRNA expression of the Nodal inhibitor Dand5 in left sensory cells. De-repression of the co-expressed Nodal drives LPM Nodal cascade induction. Here, we identify the mechanism of dand5 downregulation, finding that its posttranscriptional repression is a central process in symmetry breaking. Specifically, the RNA binding protein Bicc1 interacts with a proximal element in the 3-UTR of dand5 to repress translation in a dicer1-dependent manner. The bicc1/dicer1 module acts downstream of flow, as LRO ciliation was not affected upon its loss. Loss of bicc1 or dicer1 was rescued by parallel knockdown of dand5, placing both genes in the process of flow sensing.

developmental biology↗

A dual function of FGF signaling in Xenopus left-right axis formation

Organ left-right (LR) asymmetry is a conserved vertebrate feature, which is regulated by left-sided activation of Nodal signaling. Nodal asymmetry is established by a leftward fluid-flow generated at the ciliated LR organizer (LRO). While the role of fibroblast growth factor (FGF) signaling pathways during mesoderm development are conserved, diverging results from different model organisms suggested a non-conserved function in LR asymmetry. Here, we demonstrate that FGF is required during gastrulation in a dual function at consecutive stages of Xenopus embryonic development. In the early gastrula, FGF is necessary for LRO precursor induction, acting in parallel to FGF-mediated mesoderm induction. During late gastrulation, the FGF/Ca2+-branch is required for specification of the flow sensing lateral LRO cells, a function related to FGF-mediated mesoderm morphogenesis. This second function in addition requires input from the calcium channel Polycystin-2. Thus, analogous to mesoderm development, FGF activity is required in a dual role for laterality specification, namely for generating and sensing of leftward flow. Moreover, our data show that FGF functions in LR asymmetric development are conserved across vertebrate species, from fish to mammals.

developmental biology↗