Brian J Mitchell
Cilia Polarity The ability of ciliated epithelia to generate directed fluid flow is an important aspect of diverse developmental and physiological processes including proper respiratory function. To achieve directed flow, ciliated cells must generate 100-200 cilia that are polarized along a common axis both within and between cells. My lab is currently working towards understanding the molecular mechanisms for how cell polarity is coordinated as well as how individual cilia interpret the cell's polarity. We have determined that ciliated cells receive polarity cues via the non-canonical Wnt / Planar Cell Polarity (PCP) pathway, but the details of this are still poorly understood. Additionally, the PCP pathway is known to influence a cell's cytoskeleton dynamics and one of our main goals is to understand how this influences the ability of individual cilia to coordinate their polarity. Centriole Duplication Centrioles are microtubule based structures with nine fold symmetry that are involved in both centrosome organization and aster formation during cell division. During the normal cell cycle centrioles duplicate once, generating a mother / daughter pair, and in most post-mitotic vertebrate cells the mother centriole then goes on to form the basal body of a sensory cilium. Abnormalities in the duplication of centrioles (and centrosomes) are prevalent in many cancers suggesting a link between centriole duplication and cancer progression. While the field of cell biology has made significant advances in understanding many aspects of centriole biogenesis, the factors that limit centriole duplication remain poorly understood. My laboratory is addressing this fundamental question in cell biology from a novel direction with the use of Xenopus motile ciliated cells. Ciliated cells are unique among vertebrate cells in that they naturally generate hundreds of centrioles (basal bodies) therefore providing a great system for studying the regulation of centriole duplication. Understanding how nature has overcome the typically tight regulation of centriole duplication will lend insight into the molecular mechanisms of cancer progression. Intercalation Multiciliated cells in the skin of Xenopus embryos intitially differentiate in a distinct sub-layer of the epithelium and must undergo a short directed migration prior to intercalating into the outer epithlium. We are exploiting this reiterated developmental process to study the molecular mechanisms by which cells migrate in a directed manner and how migrating cells penetrate through epithelial barriers. We have found that this process requires a delicate regulation of cytoskeletal dynamics. We are currently exploring numerous cytoskeletal regulators to understand how cells achieve directed movement and how these cells manipulate the junctional complexes of surrounding cells to facilitate their incorporation into the skin.
Lab MembershipsMitchell Lab (Principal Investigator/Director)
Ward Building 8-090
303 E. Chicago Ave