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| John G. White
Emeritus Professor
Deparment of Anatomy and
Laboratory of Molecular Biology
227D Robert M. Bock Laboratories
Office Phone: 608-265-4813
Lab Phone: 608-265-5428
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jwhite1@facstaff.wisc.edu |
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Research Description
Studies of cell cleavage and cell polarity in Caenorhabditis elegans
The research in my laboratory is focused on two basic problems: how a cell in a developing metazoan cleaves and how the two daughter cells can acquire different fates. We are studying these processes in developing embryos of the nematode Caenorhabditis elegans. In addition, we are also developing optical instrumentation to facilitate observations of C. elegans embryos in vivo in order to visualize the dynamics of the cytoskeleton during cell cleavage.
An animal cell cleaves by the progressive constriction of an equatorial contractile ring. We are interested in how the cleavage plane is specified, how the contractile ring forms and how the daughter cells finally become pinched off.
The first few divisions of the C. elegans embryo are asymmetric and determinative. My laboratory has been studying the dynamic changes in the cytoskeleton that occur during these divisions. In the course of this work we revealed a mechanism that orients the mitotic spindle and hence the cleavage plane during determinative divisions and how polarity gets established in early blastomeres. Recent work has revealed that a molecular complex associated with the motor protein dynein is localized to a discrete focus within the cell and acts to align the mitotic spindle (Skop & White, 1998).
In addition to our studies of cell division in wild-type animals, we are also studying mutant animals in which these processes are perturbed. A genetic screen was undertaken that has yielded an interesting collection of temperature-sensitive cell division mutants. The cellular phenotypes of several of these mutants undertaken and their genes cloned. One mutant defined a gene (spd-2) that we have shown to be necessary for centrosome formation and the establishment of polarity in early embryos (O'Connell et al., 2000). Another mutant defined a different gene (zyg-1) that we have demonstrated is required for centriole and centrosome duplication in dividing cells (O'Connell et al., 2001)
Several of the cell division mutants that were isolated exhibited failures in the terminal phase of cytokinesis, i.e. cleavage furrows formed and ingressed normally, only to subsequently regress. These observations prompted a study of the terminal phase of cytokinesis. In the course of this study we demonstrated that directed secretion is necessary for the terminal phase of cytokinesis and that furthermore, this phase of cytokinesis is similar the cleavage mechanism used by plant cells (Skop et al., 2001).
Our work in optical instrumentation has been directed towards developing multiphoton imaging systems that are optimized for recording dynamic, three dimensional images from living specimens. We have shown that multiphoton microscopy gives improved viability of living specimens and can obtain images from deeper within tissue compared to confocal microscopy.
Recent Publications
Skop, A.R. and White. J.G. (1998) The dynactin complex is required for cleavage plane specification in early Caenorhabditis elegans embryos Current Biology 8: 1110-1116
O'Connell, K.F., Maxwell, K.N. and White, J.G. (2000) The spd-2 gene is required for polarization of the anterior/posterior axis and formation of the sperm asters in the Caenorhabditis elegans zygote. Dev. Biol. 222: 55-70.
Nguyen, T.Q., Sawa, H., Okano, H. and White, J.G. (2000) The C. elegans septin genes, unc-59 and unc-61, are required for normal postembryonic cytokineses and morphogenesis but have no essential function in embryogenesis. J. Cell Sci. - 113:2825-3837.
O'Connell, K.F., Caron, C, Kopish, K.R., Hurd, D. H., Kemphues, K.J., Li, Y. and White, J.G. (2001) The C. elegans zyg-1 gene encodes a novel regulator of centrosome duplication with distinct maternal and paternal roles in the embryo. Cell 105:547-558.
Skop, A.R., Bergmann, D., Mohler, W.A. and White, J.G. (2001) Completion of cytokinesis in C. elegans requires a brefeldin A-sensitive membrane accumulation at the cleavage furrow apex. Current Biol. 11:735-746.
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