Worm Breeder's Gazette 12(3): 99 (June 15, 1992)
These abstracts should not be cited in bibliographies. Material contained herein should be treated as personal communication and should be cited as such only with the consent of the author.
Six vulval precursor cells (VPCs) in the nematode C. elegans integrate at least three intercellular signals to produce an invariant pattern of differentiation into three distinct cell types (1°, 2°, and 3°). These signaling pathways are well defined by both genetic and molecular landmarks. In contrast, very little is known about how these pathways interact to specify the functions specific to each particular fate. Here we report a new mutation that defines a candidate for a 1°-specific gene - vex-1 ( sy207 )(Vulval EXecution). 85% of animals homozygous for this mutation are Egg laying defective (E g1 )and approximately 50% have protruding vulvae. Our analysis of animals containing this mutation revealed two defects in the 1° lineage First, we observed that the second of three rounds of divisions produced daughters with different sized nuclei (3/10). Second, we observed mitotic arrest in some 1° progeny attempting to complete their third round of division. We noted at least one defective mitosis in 50% of the animals lineaged (n>15). We never observed a defect in any other cell type.
To further explore the specificity of vex-1 ( sy207 ),we turned to lin-12 ,a gene that specifies the 2° VPC fate. lin-12 (d)mutations cause all VPC9 to adopt the 2° fate while lin-12 (0)mutations prevent any VPC from adopting the 2° fate. We examined the phenotype of vex-1 ( sy207 )in both lin-12 backgrounds. In the lin-12 (d)background, we found that in nine animals, 50 of 54 VPCs underwent the expected 2° lineage. The fate of the remaining four VPC was unclear, and may have been either affected by vex-1 ( sy207 )or simply indeterminate VPC fates, which are known to occur at a low frequency. In the lin-12 (0)background, five of ten animals we examined showed vex-1 ( sy207 )arrested nuclei in at least one VPC descendant. We observed arrest in any of three VPC progeny, all which normally adopt the 1° fate in this genetic background. From these data, we conclude that vex-1 ( sy207 )has a 1° specific function, which is not specific to any individual VPC.
We are working to determine the null phenotype of vex-1 to ascertain if its defects are limited solely to the 1° VPC. We have mapped vex-1 to the cluster on chromosome II and are preparing to isolate the gene to characterize its mode of action. If vex-1 is the first 1°-specific gene identified, (a 2°-specific gene, lin-11 ,has been previously identified (Ferguson, et al., Nature 326:259-267; Freyd et al., Nature 344:876-879) it will provide a powerful tool for dissecting the mechanism used to interpret the signals from the vulval developmental pathway.
Freyd et al., Nature 344:876-879)