Research Overview The Kimble lab investigates fundamental controls of animal development. Our work takes advantage of the genetic power and cellular simplicity of the nematode
Caenorhabditis elegans, which can be viewed as the “
E. coli of animal development”. Our findings rely on a variety of experimental strategies and have uncovered genes, proteins and pathways that control development in all animals, including humans.
Germline stem cells and their control Germline stem cells are maintained by a combination of signaling from their external environment or “niche” and by intrinsic regulators that promote self-renewal or differentiation. In
C. elegans, the single Distal Tip Cell (DTC) forms the niche for germline stem cells and uses Notch signaling to drive germline proliferation during development and to maintain germline stem cells in adults. Our current work focuses on how germ cells respond to Notch signaling and what molecular regulators control the decision between stem cell maintenance and differentiation.
A regulatory network controls germline fates The development of a cell as one particular cell type relies on key regulators that govern its fate. Importantly, those regulators themselves must be controlled so that cells develop in the right way and at the right time during development. Our work has outlined a molecular network that controls the decision between germline self-renewal and differentiation. Many of the regulators in the network control mRNA translation or stability, and as a result, we are particularly interested in RNA controls. We are also beginning to address how the network is modulated in response to physiological and environmental cues.
Asymmetric cell division Asymmetric cell divisions are a major mechanism for generating cell diversity during animal development. Our work centers on an asymmetric cell division that establishes polarity of the entire gonadal organ and that also generates the Distal Tip Cell (which forms the niche for germline stem cells). This pivotal asymmetric cell division is sexually dimorphic, which provides an important entrée into understanding how asymmetric cell divisions can be regulated during development and evolution.
A divergent β-catenin The Wnt signaling pathway controls many aspects of animal development. We have identified a key regulator that works as an integral component of the Wnt pathway. This regulator, called SYS-1, is a novel protein by amino acid sequence. However, SYS-1 has functional hallmarks of a β-catenin, and SYS-1 has the crystal structure of a β-catenin. Our current work explores the regulation of SYS-1 and the possibility that other divergent β-catenins exist.