An excellent model system to which to study the genetic control of development is the formation of the vulva in the nematode C. elegans. This simple developmental system can be studied at the levels of single cells (the Pn.p cells), and over twenty genes that specify Pn.p cell fate have been genetically identified. These genes may represent most of the key steps in the process of cellular determination, including signal reception, signal transduction and gene regulation. We will study the process whereby cell-cell signalling induces Pn.p cells to express vulval cell fates by analyzing two genes (lin-2 and lin-7) that are likely to interact closely with lin-10. We will also continue our molecular analysis of lin-10 itself. This combined approach should define how these three genes act to specify Pn.p cell fate. Furthermore, these studies will extend our understanding of the entire signalling pathway, because probes for these genes can be used to examine the effects of mutations in any of the other vulval determination genes. Concomitantly, we will identify new vulval determination genes by isolating mutations that suppress lin-2, lin-7 or lin-10 defects. Genetic analysis of these genes will be used to deduce how they interact to control Pn.p cell fate. The effects of these suppressor mutations can be immediately examined at the molecular level due to the concurrent molecular cloning of lin-2, lin-7 and lin-10. In addition, we will analyze lin-31 because this gene is involved in generating the developmental potential of Pn.p cells (tripotential precursor cells) as well as the subsequent specification of a particular cell fate. We will examine the functional consequences of an elimination of lin-31 activity and we will study the genetic interactions between this gene and other vulval determination genes. We will isolate the lin-31 gene in order to determine how it functions at the molecular level, and we will also examine how its activity is regulated. These studies are relevant to the control of cell proliferation. Most oncogenes cause uncontrolled cell growth by deregulating either signal transduction or gene regulation. Studies using this simple model system should further our knowledge about these processes, possibly revealing how they become deregulated and also identifying genes that may interact with disease-causing genes such as oncogenes.
| Simske, J S; Kaech, S M; Harp, S A et al. (1996) LET-23 receptor localization by the cell junction protein LIN-7 during C. elegans vulval induction. Cell 85:195-204 |
