Mechanisms of primary cilia disassembly in proliferating neuroepithelial cells

University Of Texas At Austin, Austin TX

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Abstract

DESCRIPTION (provided by applicant): Virtually all cells in vertebrates carry a primary cilium, an organelle with critical roles regulating cell signaling. Defects in cilia formation cause a rang of hereditary disorders known as ciliopathies, and signaling through cilia has recently been implicated in cancer, demonstrating the importance of this organelle for embryonic development and cellular homeostasis. However, the cilium must be disassembled for mitosis to occur, and exceedingly little is known about the mechanisms that govern this process, especially in vertebrates. This proposal will increase our understanding of cilia disassembly by examining this process in the developing Xenopus spinal cord, an optically accessible ciliated tissue that undergoes rapid proliferation. The timing and mechanism of cilia disassembly will be determined with in vivo time-lapse imaging in embryos expressing cilia and cell-cycle stage specific markers (Aim 1). The molecular mechanisms of cilia disassembly will be tested with targeted gene knockdown and overexpression studies (Aim 2). Finally, targeted bioinformatics approaches will identify likely interacting partners of these molecular regulators, and these genes will be functionally validated in vivo. This work will generate the first direct observation of cilia disassembly in vertebrates in vivo, determine the cellular and molecular mechanisms of this process in neural precursors, and characterize novel regulators of cilia disassembly, advancing the field in a number of critical areas.