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Merrill B. Hille
Migration of cells during zebrafish morphogenesis: The movement of cells is mediated by actin structures stimulated by integrins, extracellular matrix, and ligands. Migration or cell polarization is then activated by, for example, interaction of Rho GTPases and focal adhesion complexes, and/or interactions of cadherins with p120ctn and the Rho GTPases. We are studying molecules that define the pathways of cell migration and tissue migration in zebrafish embryos. These molecules include focal adhesion kinase (FAK), paxillin, zyxin, cadherins, p120ctn, and the Rho GTPases, Rho, Rac and cdc42. We have shown that phosphorylated focal adhesion kinase (FAK) is seen on tissue boundaries such as that the notochord-somite boundary and intersomitic boundaries, consistent with a role for FAK in boundary formation. We have shown using the knypek;trilobite double mutant that the polarization of FAK mRNA distribution in somite border cells is independent of internal mesenchyme cells and likely dependent on the polarization of somite border cells (Henry et al. 2000, 2001). We have also shown that the focal adhesion protein paxillin is localized in a novel manner to either adherens or tight junctions the epithelial enveloping layer of the zebrafish. FAK is also localized to these epithelial adherens or tight junctions, but is phosphorylated in a non-canonical manner, and not on Tyr-397 (Crawford et al. 2003 ). We have demonstrated the roles of p120 catenin and Rho, Rac and Cdc42 GTPases in cell polarization and the migration of presomitic mesoderm (Hsu et al., 2012). We are currently identifying the phosphorylated residues of p120 catenin that regulate cell migration or cell adhesions during early zebrafish development. One of these projects is to localize proteins that bind p120 catenin when it is phosphorylated on serine residues or tyrosine residues.
Brenda Schumpert, María Guadalupe García, Gary M. Wesel, Linda Wordeman, Merrill B. Hille 2013. Roles for focal adhesion kinase (FAK) in blastomere abscission and vesicle trafficking during cleavage in the sea urchin embryo. in press Jan 2013. Mechanisms of Develpopment
Hsu CL, Muerdter CP, Knickerbocker AD, Walsh RM, Zepeda-Rivera MA, Depner KH, Sangesland M, Cisneros TB, Kim JY, Sanchez-Vazquez P, Cherezova L, Regan RD, Bahrami NM, Gray EA, Chan AY, Chen T, Rao MY, Hille MB. 2012. Cdc42 GTPase and Rac1 GTPase act downstream of p120 catenin and require GTP exchange during gastrulation of zebrafish mesoderm. Dev Dyn. 241(10): 1545-1561.
García MG, Toney SJ, Hille MB. 2004. Focal adhesion kinase (FAK) expression and phosphorylation in sea urchin embryos. Gene Expr Patterns. 4(2): 223-234.
Crawford BD, Henry CA, Clason TA, Becker AL, Hille MB. 2003. Activity and distribution of paxillin, focal adhesion kinase, and cadherin indicate cooperative roles during zebrafish morphogenesis. Mol Biol Cell. 14(8): 3065-3081.
Henry CA, Crawford BD, Yan YL, Postlethwait J, Cooper MS, Hille MB. 2001. Roles for zebrafish focal adhesion kinase in notochord and somite morphogenesis. Dev Biol. 240(2): 474-487.
Lee SJ, Stapleton G, Greene JH, Hille MB. 2000. Protein kinase C-related kinase 2 phosphorylates the protein synthesis initiation factor eIF4E in starfish oocytes. Dev Biol. 228(2): 166-180.
Stapleton G, Nguyen CP, Lease KA, Hille MB. 1998. Phosphorylation of protein kinase C-related kinase PRK2 during meiotic maturation of starfish oocytes. Dev Biol. 193(1): 36-46.
B.A., Chemistry, with Honors; Cornell University
Ph.D., Life Sciences; The Rockefeller University, New York, NY
Postdoctoral Experience: New York University School of Medicine, New York, NY; Strangeways Research Laboratory, Cambridge, England; and University of Washington, Seattle, WA
1976 -present: Faculty, University of Washington, Departments of Zoology and Biology
1992-1993: Visiting Scientist, Whitehead Institute, MIT, Cambridge MA
1999-2000: Visiting Scientist, Institute of Neurosciences, University of Oregon, Eugene, OR