"The mammary gland functional unit develops as a result of a complex morphogenetic process organizing polarized epithelial cells into a branched network of ducts terminating in acini. Most of human breast cancers originate from transformation of epithelial cells and induce breakdown of this structure. Studies in cells grown in two-dimensional (2D) cultures have shown that microtubules target and regulate actin network and adhesion complexes, which are also known to be essential components of three-dimensional (3D) tissue architecture. Here, I propose to address microtubule functions and behavior in a more relevant system to model physiological morphogenesis. For this purpose, I intend to investigate mechanisms underlying the regulation of microtubule dynamics and their biological impact in an in vitro reconstituted acinar model of untransformed mammary epithelial cells grown in 3D. My project aims at addressing the role of the growing family of microtubule plus-end tracking proteins (+TIPs) in the control of microtubule functions during 3D mammary epithelial morphogenesis. Special focus will be given to +TIP-dependent microtubule cross-talk with key structural components of acinar architecture. Imaging of microtubules in 3D mammary epithelial culture will be used to analyze microtubule behavior during epithelial-mesenchymal transition and the role of +TIPs in this process."
Fields of science
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