The overall aim of this project is to understand how a cell cleaves in two. In particular, an understanding of the mechanisms that determine the orientation and the eccentricity of the cleavage plane will be sought. The specification of cleavage plane orientation is a fundamental aspect of cell differentiation and tissue morphogenesis. As such, it has relevance to many areas of cell and developmental biology, and to pathologies where the regulation of cell proliferation and differentiation has become perturbed, such as in tumors and many forms of congenital birth defects. Cleavage plane orientation is fundamentally linked to the polarity of a cell. If a cleavage plane bisects a polarized cell along the axis of polarity, two equivalent daughters are produced. Conversely, if the cleavage plane is orthogonal, daughters that differ in the polarizing factors will be produced.
The aim of this proposal is to continue studies of cleavage plane specification in the early embryonic cell divisions of Caenorhabditis elegans. Previous studies have revealed that rotational alignment of the mitotic apparatus is accomplished by the competitive capture of astral microtubules by a localized cortical site containing an aggregation of the dynactin complex. A combination of cell biological, genetic and molecular genetic approaches will be used to further our understanding of how cleavage planes are determined prior to the division of polarized embryonic blast cells. Specifically, three aims will be pursued: 1) to understand how a localized cortical attachment site is formed and used as a datum for rotational alignment of the mitotic apparatus; 2) to know what genes are required for rotational alignment; 3) to understand how the asters of the mitotic apparatus become differentiated in size and thereby define the eccentricity of the cleavage plane.
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