Daniel P. Kiehart

Professor of Biology

Office: 
4330 French Family Science Center, Science Drive, Duke University, Durham, NC 27708-0338
Campus Box: 
Box 90338, Dept. Biology, Duke University, Durham, NC 27708-1000
Phone: 
(919) 613-8157
Our intellectual focus is on identifying determinants of cell shape that function during development. Utilizing molecular genetic and reverse genetic approaches in Drosophila, we have shown that conventional nonmuscle myosin is necessary for driving both cell division and post-mitotic cell shape changes for morphogenesis, and cellular locomotions. Currently, we are investigating how myosin elicits cell shape change and how its function is regulated through filament formation, phosphorylation, sub-cellular targeting and small GTP-binding protein function. We are characterizing myosin light chain kinase; a novel myosin VII heavy chain; and additional elements that participate in localizing myosin and transmitting the forces that it produces. We used screens for aberrant cell shape induced in the yeast S. pombe by expression of transfected Drosophila cDNAs. These experiments show that elements that define cell shape are conserved throughout phylogeny and that a screen in yeast is a valuable tool for recovering heterologous cDNAs that encode cytoskeletal elements and the proteins that regulate them. In fly, we are identifying gene products that are necessary for myosin function by genetically recovering second site non-complementing loci and biochemically recovering proteins that bind to myosin. To date, our experiments identify ~30 loci that genetically interact with myosin and a kinase activity that phosphorylates myosin heavy chain and establish genetically, that the Rho signalling pathway is required in concert with nonmuscle myosin II for morphogenesis. We are also using manipulation studies to understand the forces that drive cellularization and morphogenesis. We show that both the amnioserosa and the leading edge of the lateral epidermis contribute to the movements of dorsal closure. Finally, we are examining the role these proteins play in movements that occur during wound healing.

Education

  • Ph.D., University of Pennsylvania 1979

  • B.A., University of Pennsylvania 1973

Franke, JD, Montague, RA, Rickoll, WL, and Kiehart, DP. "An MYH9 human disease model in flies: site-directed mutagenesis of the Drosophila non-muscle myosin II results in hypomorphic alleles with dominant character." Hum Mol Genet 16, no. 24 (December 15, 2007): 3160-3173. Full Text

Peralta, XG, Toyama, Y, Hutson, MS, Montague, R, Venakides, S, Kiehart, DP, and Edwards, GS. "Upregulation of forces and morphogenic asymmetries in dorsal closure during Drosophila development." Biophys J 92, no. 7 (April 1, 2007): 2583-2596. Full Text

Kiehart, DP, and Bloom, K. "Cell structure and dynamics." Current Opinion in Cell Biology 19, no. 1 (2007): 1-4. Full Text

Franke, JD, Boury, AL, Gerald, NJ, and Kiehart, DP. "Native nonmuscle myosin II stability and light chain binding in Drosophila melanogaster." Cell Motil Cytoskeleton 63, no. 10 (October 2006): 604-622. Full Text

Yang, Y, Kovács, M, Sakamoto, T, Zhang, F, Kiehart, DP, and Sellers, JR. "Dimerized Drosophila myosin VIIa: a processive motor." Proc Natl Acad Sci U S A 103, no. 15 (April 11, 2006): 5746-5751. Full Text

Homsy, JG, Jasper, H, Peralta, XG, Wu, H, Kiehart, DP, and Bohmann, D. "JNK signaling coordinates integrin and actin functions during Drosophila embryogenesis." Dev Dyn 235, no. 2 (February 2006): 427-434. Full Text

Kiehart, DP, Tokutake, Y, Chang, M-S, Hutson, MS, Wiemann, J, Peralta, XG, Toyama, Y, Wells, AR, Rodriguez, A, and Edwards, GS. "Ultraviolet Laser Microbeam for Dissection of Drosophila Embryos." Cell Biology, Four-Volume Set 3 (2006): 87-103. Full Text

Franke, JD, Montague, RA, and Kiehart, DP. "Nonmuscle myosin II generates forces that transmit tension and drive contraction in multiple tissues during dorsal closure." Curr Biol 15, no. 24 (December 20, 2005): 2208-2221. Full Text

Todi, SV, Franke, JD, Kiehart, DP, and Eberl, DF. "Myosin VIIA defects, which underlie the Usher 1B syndrome in humans, lead to deafness in Drosophila." Curr Biol 15, no. 9 (May 10, 2005): 862-868. Full Text

Franke, JD, Dong, F, Rickoll, WL, Kelley, MJ, and Kiehart, DP. "Rod mutations associated with MYH9-related disorders disrupt nonmuscle myosin-IIA assembly." Blood 105, no. 1 (January 1, 2005): 161-169. Full Text

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