Gastrulation shapes a vertebrate embryo from an egg-shaped aggregate of cells.In many vertebrates, massive cell divisions occur during gastrulation.In this thesis, I investigate the pattern, function, and regulation of mitotic divisions in zebrafish gastrulation. Using in vivo confocal imaging and quantitative analysis, I find that cells in dorsal axial tissues preferentially divide along the direction of tissue elongation, i.e., the anterior-posterior axis of the embryo.Establishment of the spindle polarity requires Silberblick/Wnt11, Dishevelled and Strabismus acting via the non-canonical Wnt/planar cell polarity (Wnt/PCP) pathway.On the subcellular level, oriented cell division is mediated by spindle rotation. The mitotic spindle forms at a random orientation and rotates at metaphase to line up with the anterior-posterior axis.Wnt/PCP signalling is not required for the spindle to rotate but dictates its destination.These data, together with previous work by others, demonstrate that cell polarization underlies the morphogenetic machinery that shapes the head-to-tail axis.In addition, Wnt/PCP signalling is involved in polarizing the cells, whose responses include medial-lateral elongation of the cell body and localization of protrusions, and anterior-posterior positioning of the mitotic spindle.These two types of polarized cell behaviours cooperate to shape the anterior-posterior body axis of the embryo.This work also demonstrates that the Wnt/PCP pathway is evolutionarily conserved as a strategy for cell polarization.
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Cell polarity and morphogenesis : functions and mechanisms of cell divisions in vertebrate gastrulation