Investigating plasma membrane regulation during embryonic development

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DESCRIPTION (provided by applicant): The plasma membrane plays a central role in cytokinesis and polarity, yet we know very little about how it is regulated and maintained during embryonic development. In addition, how the association between the plasma membrane and underlying cytoskeleton is dynamically transformed during the cell cycle is unclear. The plasma membrane-associated protein, dynamin has an essential yet undefined role in cytokinesis and polarity. In recent years, considerable progress has been made demonstrating that dynamin regulates a variety of membrane-cytoskeletal events. While it is evident that dynamin may regulate and even link membrane to the cytoskeleton, it is still entirely unclear how dynamin coordinates and maintains these essential events during development. The long-term goal is to better understand how the plasma membrane is regulated and maintained during embryonic development. The objective of this research program is to define and identify factors that regulate membrane-cytoskeletal events that occur during cytokinesis and polarity and to determine how dynamin coordinate these processes. The central hypothesis of the proposal is that dynamin functions to temporally and spatially control cytokinesis machinery and influence embryonic polarity. Guided by published and strong preliminary data, we plan to test our central hypothesis and accomplish the objective of this application by pursuing the following three aims: 1) Characterize the role of dynamin during cytokinesis in animal cells; and 2) Determine the contribution of dynamin during polarity maintenance; and 3) Identify and characterize cell-cycle factors critical for membrane remodeling and maintenance during embryonic development. The proposed work is innovative, because it capitalizes on a new means of identifying and characterizing the function of distinct plasma membrane domains that are highly regulated during the cell cycle. The proposed research is significant, because it is expected that the results will fundamentally advance the fields of cytokinesis, polarity as well as membrane biology. Relevance to Public Health: Understanding how the plasma membrane is regulated and maintained during development is of utmost interest because the identified factors are anticipated to provide new targets for preventive and therapeutic interventions that will aid in the growing numbers of persons who have cancer, developmental disorders and age-related abnormalities. (End of Abstract)