个人简介
Fort Lewis College, Durango, CO , B.S., 1983, Biology
University of California, Berkeley, CA, Ph.D., 1991, Zoology
University of California, San Francisco, CA , Postdoc1994-99, Anatomy, CVRI
Professional Experience:
1978-79 Undergraduate Research Student, Minority Biomedical Research Support Program (MBRS), Department of Biology, Navajo Community College, Shiprock, NM.
1981-82 Undergraduate Research Student, Minority Access to Research Careers Program (MARC), Department of Biology, Fort Lewis College, Durango, CO.
1983-91 Pre-doctoral Student, Laboratory of Dr. Richard A. Steinhardt, Department of Molecular Cell Biology, Univ. of California, Berkeley, Berkeley, CA.
1992-94 Post-graduate Researcher, Laboratory of Dr. Richard A. Steinhardt, Department of Molecular Cell Biology, Univ. of California, Berkeley, Berkeley, CA.
1994-98 Post-doctoral Fellow, Laboratory of Dr. Charles P. Ordahl, Department of Anatomy, and the Cardiovascular Research Institute, Univ. of California, San Francisco, San Francisco, CA.
1999-2000 Assistant Research Anatomist, Department of Anatomy, University of California, San Francisco, San Francisco, CA.
2000-Present Assistant Professor, Department of Biology, San Francisco State University, San Francisco, CA.
研究领域
My research uses the chicken embryo to study cellular and molecular regulators in early myotome formation, also called the primitive skeletal muscle, in transient organs called somites. Briefly, somites are produced from the segmental plate mesoderm as paired ball-like structures on either side of the neural tube. They quickly increase in size and undergo dorso-ventral and medio-lateral pattern formation to form the myotome about 10.5 hours later. The process of myotome formation results from the interplay of molecular signals secreted by adjacent tissues near the somites so that complex signaling patterns are created to specify the cells in somites towards different tissue fates such as bone, skin, or skeletal muscle.
Some of these signaling molecules are secreted morphogens that include the Wnt proteins, sonic hedgehog, and bone morphogen proteins. Although morphogen gradients provide a molecular explanation for early skeletal muscle development, it falls short as a model because it excludes the role played by cells in mediating the signaling process. There is little information known about cellular behaviors at times when morphogens signal the somite for myotome formation and this represents a hole in our current knowledge of the myotome formation process.
The Denetclaw lab investigates dynamic changes in cells that could be interpreted as signaling mechanisms for early skeletal myogenesis. For instance, we have observed the development of large numbers of filopodia that are produced by dermomyotome cells and that extend to the immediate overlying ectoderm cell layer. These filopodia are absent in newly formed somites, but after somite dorso-ventral patterning, they form on the medial side of the dermomyotome which is the same area where the myotome are first produced.
The Denetclaw lab investigates dynamic changes in cells that could be interpreted as signaling mechanisms for early skeletal myogenesis. For instance, we have observed the development of large numbers of filopodia that are produced by dermomyotome cells and that extend to the immediate overlying ectoderm cell layer. These filopodia are absent in newly formed somites, but after somite dorso-ventral patterning, they form on the medial side of the dermomyotome which is the same area where the myotome are first produced.
We hypothesize that there is direct connection between filopodia development and the formation of the myotome. My lab is studying ectoderm signaling of the dermomyotome using a variety of techniques such as live somite imaging by confocal microscopy and by high resolution imaging using the transmission electron microscope.
In addition, we use embryo microsurgery and tissue transplantation, and animal cell culture. Our findings show signaling between the ectoderm and dermomyotome that involves the transfer of membrane micro-domains, or lipid rafts, and a role in the development of the myotome.
Lipid rafts are small membrane platforms associated with proteins that move within the fluid membrane plane as a unit structure. Lipid rafts have recently gained importance in terms of biological function. For example, lipid rafts are active regulators mediating signal transduction events at cell membranes and have other roles like mediating intracellular vesicle transport and synapse formation.
Our research is funded by the NIH-RIMI2 Health Disparities Research and Training Grant and I am one of two faculty investigators at SFSU supported by this grant. I also collaborate with Dr. Walter Holleran at the San Francisco Veteran Affairs Hospital where my students receive electron microscopy training and have research opportunities in his laboratory. In summary, my research proposes to investigate the ectoderm–dermomyotome signaling connection and the role of membrane micro-domains, or lipid rafts, in the regulation of myotome formation in somites.
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1. Fong, P., Turner, P.R., Denetclaw, W.F., and Steinhardt, R.A. (1990). Increased activity of calcium leak channels in myotubes of Duchenne human and mdx mouse origin. Science. 250:673-676.
2. Turner, P.R., Fong, P., Denetclaw, W.F., and Steinhardt, R.A. (1991). Increased calcium influx in dystrophic muscle. Journal of Cell Biology. 115(6):1701-12.
3. Denetclaw, W.F. Jr., Bi, G., Pham, D.V., and Steinhardt, R.A. (1993). Heterokaryon myotubes with normal mouse and Duchenne nuclei exhibit sarcolemmal dystrophin staining and efficient intracellular free calcium control. Molecular Biology of the Cell. 4:963-972.
4. Denetclaw, W.F. Jr., and Denetclaw, T.H. (1994). Is "south-west US mystery disease" caused by hantavirus? The Lancet. 343(8888):53-54.
5. Denetclaw, T.H. and Denetclaw, W.F. Jr. (1994). Hantavirus Pulmonary Syndrome in New England and Europe. New England Journal of Medicine. 331(8):545-548.
6. Denetclaw, W.F. Jr., Hopf, F.W., Cox, G.A., Chamberlain, J.S., and Steinhardt, R.A. (1994). Myotubes from transgenic mdx mice expressing full-length dystrophin show normal calcium regulation. Molecular Biology of the Cell. 5:1159-1167.
7. Garrison, E.R., Denetclaw, W.F. Jr., and Scott, O.T. (1995). Navajo scientists of the next century -- Laanaa Daniidzin. Journal of Navajo Education. 12(3):11-15.
8. McCarter, G.C., Denetclaw, W.F. Jr., Reddy, P., and Steinhardt, R.A. (1997). Lipofection of the dystrophin gene lowers intracellular free calcium and calcium leak channel activity in mdx myotubes. Gene Therapy 4(5):483-487.
9. Denetclaw, W.F. Jr., Christ, B., and Ordahl, C.P. (1997). Location and growth of epaxial myotome precursor cells. Development. 124:1601-1610.
10. Dettman, R. W., Denetclaw, W. Jr., Ordahl, C.P., and Bristow, J. (1998). Common epicardial origin of coronary vascular smooth muscle, perivascular fibroblasts, and intermyocardial fibroblasts in the avian heart. Developmental Biology. 193:169-181.
11. Ordahl, C.P., Williams, B., and Denetclaw, W.F. Jr. (2000). Lineage and determination in the myotome. Current Topics in Developmental Biology, Vol. 47:Somitogenesis (Part II).
12. Denetclaw, W.F. Jr. and Ordahl, C.P. (2000). The growth of the dermomyotome and formation of early myotome lineages in thoracolumbar somites of chicken embryos. Development 127:893-905.
13. Ordahl C.P., Berdougo E., Venters S.J., Denetclaw W.F. (2001). The dermomyotome dorsomedial lip drives growth and morphogenesis of both the primary myotome and dermomyotome epithelium. Development 128:1731-44.
14. Denetclaw W.F., Berdougo E., Venters S.J., Ordahl C.P. (2001). Morphogenetic cell movements in the middle region of the dermomyotome dorsomedial lip associated with patterning and growth of the primary epaxial myotome. Development 128:1745-55.
15. Galli LM, Willert K, Nusse R, Yablonka-Reuveni Z, Nohno T, Denetclaw W, and Burrus LW. (2004). A proliferative role for Wnt-3a in chick somites. Dev Biol. 269(2):489-504.
16. Venters SJ, Argent RE, Deegan FM, Perez-Baron G, Wong TS, Tidyman WE, Denetclaw WF Jr, Marcelle C, Bronner-Fraser M, and Ordahl CP. (2004). Precocious terminal differentiation of premigratory limb muscle precursor cells requires positive signalling. Dev Dyn. 229(3):591-9.
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