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The let-60 locus controls the switch between vulval and nonvulval cell fates in Caenorhabditis elegans

Han, Min and Aroian, Raffi V. and Sternberg, Paul W. (1990) The let-60 locus controls the switch between vulval and nonvulval cell fates in Caenorhabditis elegans. Genetics, 126 (4). pp. 899-913. ISSN 0016-6731. PMCID PMC1204287. https://resolver.caltech.edu/CaltechAUTHORS:20190515-145312907

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Abstract

During induction of the Caenorhabditis elegans hermaphrodite vulva by the anchor cell of the gonad, six multipotent vulval precursor cells (VPCs) have two distinct fates: three VPCs generate the vulva and the other three VPCs generate nonspecialized hypodermis. Genes that control the fates of the VPCs in response to the anchor cell signal are defined by mutations that cause all six VPCs to generate vulval tissue (Multivulva or Muv) or that cause all six VPCs to generate hypodermis (Vulvaless or Vul). Seven dominant Vul mutations were isolated as dominant suppressors of a lin-15 Muv mutation. These mutations are dominant alleles of the gene let-60, previously identified only by recessive lethal mutations. Our genetic studies of these dominant Vul recessive lethal mutations, recessive lethal mutations, intragenic revertants of the dominant Vul mutations, and the closely mapping semi-dominant multivulva lin-34 mutations suggest that: (1) loss-of-function mutations of let-60 are recessive lethal at a larval stage, but they also cause a Vul phenotype if the lethality is rescued maternally by a lin-34 gain-of-function mutation. (2) The dominant Vul alleles of let-60 are dominant negative mutations whose gene products compete with wild-type activity. (3) lin-34 semidominant Muv alleles are either gain-of-function mutations of let-60 or gain-of-function mutations of an intimately related gene that elevates let-60 activity. We propose that let-60 activity controls VPC fates. In a wild-type animal, reception by a VPC of inductive signal activates let-60, and it generates into a vulval cell type; in absence of inductive signal, let-60 activity is low and the VPC generates hypodermal cells. Our genetic interaction studies suggest that let-60 acts downstream of let-23 and lin-15 and upstream of lin-1 and lin-12 in the genetic pathway specifying the switch between vulval and nonvulval cell types.


Item Type:Article
Related URLs:
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https://www.genetics.org/content/126/4/899.longPublisherArticle
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1204287PubMed CentralArticle
ORCID:
AuthorORCID
Sternberg, Paul W.0000-0002-7699-0173
Additional Information:© 1990 by the Genetics Society of America. Manuscript received July 5, 1990; Accepted for publication August 23, 1990. We thank R. Rogge for isolating several of the lin-15 suppressors, Y. Hadju and A. Holboke for handling our strain collection, G. Beitel, S. Clark, R. Horvitz, G. Jongeward, and H. Chamberlin for communicating unpublished results on let-60 and lin-34, R. Herman and E. Hedgecock for communicating results on mosaic analysis on lin-15, D. Clark and D. Baillie for providing us with strains with let-60 and other lethal alleles, the Caenorhabditis elegans Genetic Center (supported by a contract between the National Institutes of Health Division of Research Resources and Curators of the University of Missouri) and R. Horvitz’s laboratory for many useful strains, and R. Hill, G. Jongeward, and others in our laboratory for strains and stimulating discussions. We thank H. Lipshitz, S. Parkhurst, J. Hodgkin, S. Kim, R. Herman, R. Horvitz, I. Greenwald, C. Kenyon, H. Mori, H. Chamberlin and other members of our laboratory for comments on the manuscript. M.H. is a Genentech Fellow of the Life Science Research Foundation. R.V.A. was a U.S. Public Health Service trainee. P.W.S. is an investigator of the Howard Hughes Medical Institute, a Searle Scholar, and a Presidential Young Investigator of the National Science Foundation. This research has been supported by grants to P.W.S. from the U.S. Public Health Service (HD23690) and the March of Dimes Birth Defects Foundation.
Funders:
Funding AgencyGrant Number
Life Science Research FoundationUNSPECIFIED
Howard Hughes Medical Institute (HHMI)UNSPECIFIED
Searle Scholars ProgramUNSPECIFIED
NSFUNSPECIFIED
NIHHD23690
March of Dimes Birth Defects FoundationUNSPECIFIED
Issue or Number:4
PubMed Central ID:PMC1204287
Record Number:CaltechAUTHORS:20190515-145312907
Persistent URL:https://resolver.caltech.edu/CaltechAUTHORS:20190515-145312907
Official Citation:The let-60 locus controls the switch between vulval and nonvulval cell fates in Caenorhabditis elegans. M Han, R V Aroian and P W Sternberg. GENETICS December 1, 1990 vol. 126 no. 4 899-913
Usage Policy:No commercial reproduction, distribution, display or performance rights in this work are provided.
ID Code:95521
Collection:CaltechAUTHORS
Deposited By: Tony Diaz
Deposited On:16 May 2019 02:39
Last Modified:03 Oct 2019 21:14

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