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Cell Adhesion and Tissue Patterning
Masatoshi Takeichi Ph.D.



Animal cells organize into tissues with complex architecture. Our lab is exploring the molecular mechanisms by which individual cells assemble into a tissue-specific multicellular structure, such as epithelial sheets and neural networks. We are also interested in the molecular basis of how tissue architecture is disrupted during carcinogenesis, a process that is thought to accelerate the metastasis of cancer cells. For these studies, we are focusing on the roles played by cell-cell adhesion and recognition molecules, the cadherin family of adhesion molecules in particular, as these are known to be indispensable for tissue construction. Our current studies are divided into three categories:

1) Cell-cell adhesion is a dynamic process, and this nature of cell-cell adhesion is implicated in various cell behaviors, such as contact-dependent regulation of cell movement and cancer metastasis. A growing body of evidence suggests that cadherins cooperate with cytoskeletal and/or motility machineries, such as actin regulators, non-muscle myosins, and Rho GTPases, in modulating cell assembly. We are therefore studying the molecular mechanisms underlying the crosstalk between cadherins and such cytoskeletal systems.

2) A second area of interest to our lab is to gain a better understanding of how the cell-cell adhesion machinery contributes to animal morphogenesis. Using mouse and chicken embryos, we are analyzing the roles of cadherins and associated proteins in various morphogenetic processes, including neural tube closure and neural crest migration. We are also investigating the roles of members of the cadherin superfamily known as protocadherins, deficiencies of which have been implicated in brain disorders. Through these studies, we expect to gain deeper mechanistic insights into the ways by which cells build the elaborate structures of the animal body.

3) In addition, we have recently begun analyzing the functions of microtubule minus end-associated proteins, Nezha/CAMSAPs. These proteins regulate microtubule assembly patterns, centrosomal function, and organelle positioning. We are exploring molecular mechanisms underlying such regulatory activity, as well as the roles of these molecules in cellular morphogenesis, such as polarized epithelial formation and axon growth, with the aim of uncovering novel functions of non-centrosomal microtubules.

 























Select references

Nagae S, et al. Non-centrosomal microtubules regulate F-actin organization through the suppression of GEF-H1 activity. Genes Cells 18.387-96 (2013)

Tanaka N, et al. Nezha/CAMSAP3 and CAMSAP2 cooperate in epithelial-specific organization of noncentrosomal microtubules. Proc Natl Acad Sci U S A 49.20029-34 (2012)

Nishimura T, et al. Planar cell polarity links axes of spatial dynamics in neural-tube closure. Cell 149.1084-97 (2012)

Ishiuchi T. and Takeichi M. Willin and Par3 cooperatively regulate epithelial apical constriction through aPKC-mediated ROCK phosphorylation. Nat Cell Biol 13.860-6 (2011)

Taguchi K, et al. Mechanosensitive EPLIN-dependent remodeling of adherens junctions regulates epithelial reshaping. J Cell Biol 194.643-56 (2011)

Ishiuchi T, et al. Mammalian Fat and Dachsous cadherins regulate apical membrane organization in the embryonic cerebral cortex. J Cell Biol 185. 959-67 (2009)

Meng W, et al. Anchorage of microtubule minus ends to adherens junctions regulates epithelial cell-cell contacts. Cell 135. 948-59 (2008)