Src homology-2 (SH2) domain-containing protein tyrosine phosphatases (SHPs) have been identified as either positive or negative regulators of signaling events downstream of receptor protein tyrosine kinases (R-PTKs). We describe here our characterization of ptp-2, a Caenorhabditis elegans gene that encodes a 668-amino-acid SHP. We isolated a recessive ptp-2 loss-of-function allele, op194, that ...

Large gaps in basement membrane occur at sites of cell invasion and tissue remodelling in development and cancer. Though never followed directly in vivo, basement membrane dissolution or reduced synthesis have been postulated to create these gaps. Using landmark photobleaching and optical highlighting of laminin and type IV collagen, we find that a new mechanism, basement membrane sliding, unde...

Development of the C. elegans vulva requires coordination between a strikingly complex set of molecular regulators and pathways. In particular, the correct specification of vulval cell-fates requires both the activation of RTK/Ras/Map kinase members as well as negative regulation by a set of genes known as the SynMuvs. SynMuvs comprise two functionally redundant sets of genes that appear to ant...

During vulval development in Caenorhabditis elegans, six precursor cells acquire a spatial pattern of distinct cell fates. This process is guided by a gradient in the soluble factor, LIN-3, and by direct interactions between neighboring cells mediated by the Notch-like receptor, LIN-12. Genetic evidence has revealed that these two extracellular signals are coupled: lateral cell-cell interaction...

The two serotonergic HSN motor neurons of the nematode Caenorhabditis elegans innervate the vulval muscles and stimulate egg laying by hermaphrodites. By analyzing mutant and laser-operated animals, we find that both epithelial cells of the developing vulva and axons of the ventral nerve cord are required for HSN axonal guidance. Vulval precursor cells help guide the growth cone of the emerging...

Vulval intraepithelial neoplasia (VIN) is thought to be the premalignant phase of human papillomavirus (HPV)-associated vulval squamous cell carcinoma (VSCC). Various molecular events have been suggested as markers for progression from VIN to VSCC, but loss of heterozygosity (LOH) in vulval neoplasia has rarely been studied in this context. We performed LOH analysis by polymerase chain reaction...

Caenorhabditis elegans vulval development culminates during exit from the L4-to-adult molt with the formation of an opening through the adult hypodermis and cuticle that is used for egg laying and mating. Vulva formation requires the heterochronic gene lin-29, which triggers hypodermal cell terminal differentiation during the final molt. lin-29 mutants are unable to lay eggs or mate because no ...

During development of the Caenorhabditis elegans hermaphrodite, the gonadal anchor cell induces nearby Pn.p cells to adopt vulval fates. The response to this signal is mediated by a receptor tyrosine kinase signal transduction pathway that has been remarkably well conserved during metazoan evolution. Because mitogen-activated protein (MAP) kinases are activated by receptor tyrosine kinase pathw...