The Kimble Laboratory
Faculty > Judith E. Kimble
Judith E. Kimble
Professor, Biochemistry
jekimble@facstaff.wisc.edu
Research Description
Our lab focuses on controls of germline stem cells in the nematode C. elegans.
Some years ago, we showed that germline stem cells (GSC) are controlled by Notch signaling from a single-celled somatic niche (Kimble and White 1981). More recently, we have focused on genes that act downstream of Notch signaling to maintain germ cells in a stem cell state or drive them into differentiation.
Most notably, a PUF RNA-binding protein called FBF is essential for GSC maintenance (Crittenden et al 2002). PUF RNA-binding proteins bind regulatory elements in the 3’untranslaged region of target mRNAs, and repress their expression, either promoting mRNA degradation or inhibiting mRNA translation (e.g. Wickens et al 2002). FBF can either repress expression of differentiation regulators (Crittenden et al 2002) or maintain a low level of dose-sensitive proliferation regulators (Thompson et al 2005).
An increasing complex regulatory network is emerging that controls proliferation or differentiation. This network is both robust and plastic. Thus, no single component is essential for GSC maintenance or differentiation, but changing any single component can contract or expand the number of germ cells that divide mitoticaly before differentiating (Kimble and Crittenden 2007).
Both Notch signaling and PUF RNA-binding proteins control stem cells more broadly, suggesting that understanding the C. elegans germlien may shed light on fundamental stem cell controls.
Selected References
Kimble JE, White JG. On the control of germ cell development in Caenorhabditis elegans. Developmental Biology 81:208-219. 1981.
Crittenden SL, Bernstein DS, Bachorik JL, Thompson BE, Gallegos M, Petcherski AG, Moulder G, Barstead R, Wickens M, Kimble J. A conserved RNA-binding protein controls germline stem cells in Caenorhabditis elegans. Nature 417:660-663. 2002.
Wickens M, Bernstein DS, Kimble J, Parker R. A PUF family portrait: 3'UTR regulation as a way of life. Trends in Genetics 18(3):150-157. 2002.
Thompson BE, Bernstein DS, Bachorik JL, Petcherski AG, Wickens M, Kimble J. Dose-dependent control of proliferation and sperm specification by FOG-1/CPEB. Development 132:3471-3481. 2005.
Kimble J, Crittenden S. Controls of germline stem cells, entry into meiosis and the sperm/oocyte decision in C. elegans. Ann. Rev. Cell Dev. Biol. 23. In press.