Matthew Buechner, Assistant Professor, Ph.D., Molecular Biology,
University of Wisconsin-Madison, 1990.
EMail Matthew
Why are capillaries narrower than an aorta? What regulates the diameter of the various segments of the long nephrons in our kidneys? My research studies the mechanisms used by epithelial cells to measure and regulate the diameter of small tubules. We use the tiny roundworm Caenorhabditis elegans to look at a series of genes whose function is required to prevent its tubules from swelling into fluid-filled cysts. This roundworm grows quickly on a bacterial lawn on Petri plates, and is clear, so we can watch the development and growth of its renal tubules (called the excretory canals) in living creatures.
In a series of mutations in 12 genes named exc, the hollow renal tubules swell into large fluid-filled cysts. The mutants are defective in molecules normally located on the inner (apical) surface of the cell, surrounding the hollow lumen through which liquid passes to be expelled. Seven of these genes have now been cloned, and identify the cytoskeletal protein spectrin, an activator of the cytoskeletal regulator CDC42, a secreted mucin, two ion channels, a peptidase, and a molecule involved in mRNA processing. These proteins work together to regulate the diameter of the canals both spatially and over the course of development. The remaining exc genes have been well-mapped, and students in my laboratory are currently cloning these genes by means of mutant rescue with DNA provided by the C. elegans genome sequencing project. We are now using genetics and immuno-electron microscopy to determine how these components work together to regulate simultaneously the function and structure of the hollow excretory canals.
As a related project, we are looking at the nematode homologues of human genes defective in polycystic kidney and liver diseases (PKD and PCLD). These are surprisingly common genetic diseases, in which various tubules swell into large fluid-filled cysts over the course of years, and often culminate in complete renal, liver and pancreatic failure as well as cerebral aneurysms. We are now using genetic, biochemical, and electrophysiological techniques to investigate the relationship between the nematode and human proteins.
Representative Publications:
Buechner, M. 2002. Tubes and the single C. elegans excretory cell. Trends in Cell Biology 12; 479-484.
Fujita, M, D. Hawkinson, K.V. King, D.H. Hall, H. Sakamoto, & M. Buechner. 2003. The Role of the ELAV Homologue EXC-7 in the Development of the Caenorhabditis elegans Excretory Canals. Developmental Biology, in press.
Kaletta, T., M. Van Der Craen, A. Van Geel, N. Dewulf, T. Bogaert, M. Branden, K.V. King, M. Buechner, R. Barstead, D. Hyink, H.P. Li, L. Geng, C. Burrow, & P. Wilson. 2003. Towards understanding the polycystins. Nephron 93, E9-E17.
Suzuki, N., M. Buechner, K. Nishiwaki, D.H. Hall, H. Nakanishi, Y. Takai, N. Hisamoto, & K. Matsumoto. 2001. A putative GDP-GTP exchange factor is required for development of the excretory cell in Caenorhabditis elegans. EMBO Reports 2, 530-535.
Buechner, M., D.H. Hall, H. Bhatt, & E.M. Hedgecock. 1999. Cystic Canal Mutants in Caenorhabditis elegans Are Defective in the Apical Membrane Domain of the Renal (Excretory) Cell. Developmental Biology 214:227-241.