Dynamic intracellular distribution of Vangl2 during cell polarization in zebrafish gastrula

During vertebrate gastrulation, convergence and extension movements elongate embryonic tissues anteroposteriorly and narrow them mediolaterally. Planar Cell Polarity (PCP) signaling is essential for mediolateral cell elongation underlying these movements, but how this polarity arises is poorly understood. We analyzed cell elongation, orientation, and migration behaviors of lateral mesodermal cells undergoing convergence and extension movements in wild-type embryos and mutants for the Wnt/PCP core component Trilobite/Vangl2. We demonstrate that Vangl2 function is required at the time when cells transition to a highly elongated and mediolaterally aligned body. We show that tri/vangl2 mutant cells fail to undergo this transition and to migrate along a straight path and high net speed towards the dorsal midline. Instead, tri/vangl2 mutant cells exhibit an anterior/animal pole bias in their cell body alignment and movement direction, suggesting that PCP signaling promotes effective dorsal migration in part by suppressing anterior/animalward cell polarity and movement. Endogenous Vangl2 protein accumulates at the plasma membrane of mesenchymal converging cells at the time its function is required for mediolaterally polarized cell behavior. Heterochronic cell transplantations demonstrated that Vangl2 cell membrane accumulation is stage dependent, and regulated by both intrinsic factors and an extracellular signal, which is distinct from PCP signaling or other gastrulation regulators, including BMP and Nodals. Moreover, mosaic expression of fusion proteins revealed enrichment of Vangl2 at the anterior cell edges of highly mediolaterally elongated cells, consistent with the PCP pathway core components’ asymmetric distribution in Drosophila and vertebrate epithelia.

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