Extracellular regulation of Xenopus development

Summary Cell-cell communication in the early embryo specifies cell fates and orchestrates collective cell movements. One of the main drivers of collective cell behaviors in vertebrates is the core planar cell polarity (PCP) pathway. Genetic studies demonstrated the requirement for vertebrate PCP proteins in many morphogenetic processes including neural tube closure. Our preliminary data revealed the anteroposterior and the mediolateral axes of PCP in the Xenopus neuroectoderm that are marked, respectively, by Vangl2 and Diversin protein clusters. The proposed study will test a hypothesis that the two orthogonal PCP axes are mediated by distinct signaling pathways. This will be achieved using a combination of cell biological, proteomic and live imaging approaches in Xenopus, a powerful experimental model allowing rapid functional analysis in vivo. The medially-enriched PCP clusters will be studied by identifying Diversin- interacting proteins and correlating the dynamics of their assembly and localization with Myosin II-dependent cell behaviors in the neural plate and epidermal ectoderm. The regulation of the anteriorly-enriched PCP clusters and neural tube folding by fibroblast growth factor (FGF) signaling will be investigated and the relevant structural motifs and intracellular pathways will be defined. Wild-type Vangl2 will be compared to mutated Vangl2 constructs that are not sensitive to FGF signaling. The proposed study will reveal the relative contributions of secreted growth factors and actomyosin contractility to morphogenesis in early vertebrate embryos. These experiments will expand the knowledge of morphogenetic mechanisms that are critical for normal development and often disrupted in disease.