Genetics, Vol 126, 899-913, Copyright © 1990


INVESTIGATIONS

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
Howard Hughes Medical Institute, Division of Biology, California Institute of Technology, Pasadena, California 91125

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 semidominant 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.


This article has been cited by other articles:


Home page
GeneticsHome page
C. E. Rocheleau, K. Cullison, K. Huang, Y. Bernstein, A. C. Spilker, and M. V. Sundaram
The Caenorhabditis elegans ekl (Enhancer of ksr-1 Lethality) Genes Include Putative Components of a Germline Small RNA Pathway
Genetics, March 1, 2008; 178(3): 1431 - 1443.
[Abstract] [Full Text] [PDF]


Home page
GeneticsHome page
M.-H. Lee, M. Ohmachi, S. Arur, S. Nayak, R. Francis, D. Church, E. Lambie, and T. Schedl
Multiple Functions and Dynamic Activation of MPK-1 Extracellular Signal-Regulated Kinase Signaling in Caenorhabditis elegans Germline Development
Genetics, December 1, 2007; 177(4): 2039 - 2062.
[Abstract] [Full Text] [PDF]


Home page
DevelopmentHome page
W. Zhong and P. W. Sternberg
Automated data integration for developmental biological research
Development, September 15, 2007; 134(18): 3227 - 3238.
[Abstract] [Full Text] [PDF]


Home page
Mol. Cell. Biol.Home page
K. Modzelewska, M. G. Elgort, J. Huang, G. Jongeward, A. Lauritzen, C. H. Yoon, P. W. Sternberg, and N. Moghal
An Activating Mutation in sos-1 Identifies Its Dbl Domain as a Critical Inhibitor of the Epidermal Growth Factor Receptor Pathway during Caenorhabditis elegans Vulval Development
Mol. Cell. Biol., May 15, 2007; 27(10): 3695 - 3707.
[Abstract] [Full Text] [PDF]


Home page
GeneticsHome page
M. M. Harrison, X. Lu, and H. R. Horvitz
LIN-61, One of Two Caenorhabditis elegans Malignant-Brain-Tumor-Repeat-Containing Proteins, Acts With the DRM and NuRD-Like Protein Complexes in Vulval Development but Not in Certain Other Biological Processes
Genetics, May 1, 2007; 176(1): 255 - 271.
[Abstract] [Full Text] [PDF]


Home page
GeneticsHome page
B. P. Gupta, J. Liu, B. J. Hwang, N. Moghal, and P. W. Sternberg
sli-3 Negatively Regulates the LET-23/Epidermal Growth Factor Receptor-Mediated Vulval Induction Pathway in Caenorhabditis elegans
Genetics, November 1, 2006; 174(3): 1315 - 1326.
[Abstract] [Full Text] [PDF]


Home page
DevelopmentHome page
E. C. Andersen, X. Lu, and H. R. Horvitz
C. elegans ISWI and NURF301 antagonize an Rb-like pathway in the determination of multiple cell fates
Development, July 15, 2006; 133(14): 2695 - 2704.
[Abstract] [Full Text] [PDF]


Home page
GeneticsHome page
P. W. Sternberg
Pathway to RAS.
Genetics, February 1, 2006; 172(2): 727 - 731.
[Full Text] [PDF]


Home page
Genes Dev.Home page
M. V. Sundaram
The love-hate relationship between Ras and Notch
Genes & Dev., August 15, 2005; 19(16): 1825 - 1839.
[Abstract] [Full Text] [PDF]


Home page
DevelopmentHome page
N. Moghal, L. R. Garcia, L. A. Khan, K. Iwasaki, and P. W. Sternberg
Modulation of EGF receptor-mediated vulva development by the heterotrimeric G-protein G{alpha}q and excitable cells in C. elegans
Development, October 1, 2003; 130(19): 4553 - 4566.
[Abstract] [Full Text] [PDF]


Home page
Proc. Natl. Acad. Sci. USAHome page
J. Czyzyk, J. L. Brogdon, A. Badou, O. Henegariu, P. Preston Hurlburt, R. Flavell, and K. Bottomly
Activation of CD4 T cells by Raf-independent effectors of Ras
PNAS, May 13, 2003; 100(10): 6003 - 6008.
[Abstract] [Full Text] [PDF]


Home page
Genes Dev.Home page
J. E. Gleason, H. C. Korswagen, and D. M. Eisenmann
Activation of Wnt signaling bypasses the requirement for RTK/Ras signaling during C. elegans vulval induction
Genes & Dev., May 15, 2002; 16(10): 1281 - 1290.
[Abstract] [Full Text] [PDF]


Home page
GeneticsHome page
C. E. Rocheleau, R. M. Howard, A. P. Goldman, M. L. Volk, L. J. Girard, and M. V. Sundaram
A lin-45 raf Enhancer Screen Identifies eor-1, eor-2 and Unusual Alleles of Ras Pathway Genes in Caenorhabditis elegans
Genetics, May 1, 2002; 161(1): 121 - 131.
[Abstract] [Full Text] [PDF]


Home page
Mol. Cell. Biol.Home page
J. L. Schutzman, C. Z. Borland, J. C. Newman, M. K. Robinson, M. Kokel, and M. J. Stern
The Caenorhabditis elegans EGL-15 Signaling Pathway Implicates a DOS-Like Multisubstrate Adaptor Protein in Fibroblast Growth Factor Signal Transduction
Mol. Cell. Biol., December 1, 2001; 21(23): 8104 - 8116.
[Abstract] [Full Text] [PDF]


Home page
DevelopmentHome page
Z. Chen and M. Han
Role of C. elegans lin-40 MTA in vulval fate specification and morphogenesis
Development, December 1, 2001; 128(23): 4911 - 4921.
[Abstract] [Full Text] [PDF]


Home page
GeneticsHome page
L. Nilsson, T. Tiensuu, and S. Tuck
Caenorhabditis elegans lin-25: A Study of Its Role in Multiple Cell Fate Specification Events Involving Ras and the Identification and Characterization of Evolutionarily Conserved Domains
Genetics, November 1, 2000; 156(3): 1083 - 1096.
[Abstract] [Full Text]


Home page
Mol. Biol. CellHome page
C. H. Yoon, C. Chang, N. A. Hopper, G. M. Lesa, and P. W. Sternberg
Requirements of Multiple Domains of SLI-1, a Caenorhabditis elegans Homologue of c-Cbl, and an Inhibitory Tyrosine in LET-23 in Regulating Vulval Differentiation
Mol. Biol. Cell, November 1, 2000; 11(11): 4019 - 4031.
[Abstract] [Full Text]


Home page
GeneticsHome page
J. Liu, P. Tzou, R. J. Hill, and P. W. Sternberg
Structural Requirements for the Tissue-Specific and Tissue-General Functions of the Caenorhabditis elegans Epidermal Growth Factor LIN-3
Genetics, November 1, 1999; 153(3): 1257 - 1269.
[Abstract] [Full Text]


Home page
J. Biol. Chem.Home page
L. A. Aramli and C. M. Teschke
Single Amino Acid Substitutions Globally Suppress the Folding Defects of Temperature-sensitive Folding Mutants of Phage P22 Coat Protein
J. Biol. Chem., August 6, 1999; 274(32): 22217 - 22224.
[Abstract] [Full Text] [PDF]


Home page
Mol. Cell. Biol.Home page
S. Stewart, M. Sundaram, Y. Zhang, J. Lee, M. Han, and K.-L. Guan
Kinase Suppressor of Ras Forms a Multiprotein Signaling Complex and Modulates MEK Localization
Mol. Cell. Biol., August 1, 1999; 19(8): 5523 - 5534.
[Abstract] [Full Text] [PDF]


Home page
Mol. Cell. Biol.Home page
T. Gu, S. Orita, and M. Han
Caenorhabditis elegans SUR-5, a Novel but Conserved Protein, Negatively Regulates LET-60 Ras Activity during Vulval Induction
Mol. Cell. Biol., August 1, 1998; 18(8): 4556 - 4564.
[Abstract] [Full Text]


Home page
GeneticsHome page
D. Jacobs, G. J. Beitel, S. G. Clark, H. R. Horvitz, and K. Kornfeld
Gain-of-Function Mutations in the Caenorhabditis elegans lin-1 ETS Gene Identify a C-Terminal Regulatory Domain Phosphorylated by ERK MAP Kinase
Genetics, August 1, 1998; 149(4): 1809 - 1822.
[Abstract] [Full Text] [PDF]


Home page
DevelopmentHome page
D. Eisenmann, J. Maloof, J. Simske, C Kenyon, and S. Kim
The beta-catenin homolog BAR-1 and LET-60 Ras coordinately regulate the Hox gene lin-39 during Caenorhabditis elegans vulval development
Development, January 9, 1998; 125(18): 3667 - 3680.
[Abstract] [PDF]


Home page
DevelopmentHome page
D Levitan and I Greenwald
LIN-12 protein expression and localization during vulval development in C. elegans
Development, January 8, 1998; 125(16): 3101 - 3109.
[Abstract] [PDF]


Home page
DevelopmentHome page
J. Maloof and C Kenyon
The Hox gene lin-39 is required during C. elegans vulval induction to select the outcome of Ras signaling
Development, January 1, 1998; 125(2): 181 - 190.
[Abstract] [PDF]


Home page
Genes Dev.Home page
A. Hajnal, C. W. Whitfield, and S. K. Kim
Inhibition of Caenorhabditis elegans vulval induction by gap-1 and by let-23 receptor tyrosine kinase
Genes & Dev., October 15, 1997; 11(20): 2715 - 2728.
[Abstract] [Full Text] [PDF]


Home page
J. Biol. Chem.Home page
H. Ueno, K. Sasaki, K. Miyagawa, H. Honda, K. Mitani, Y. Yazaki, and H. Hirai
Antisense Repression of Proto-oncogene c-Cbl Enhances Activation of the JAK-STAT Pathway but Not the Ras Pathway in Epidermal Growth Factor Receptor Signaling
J. Biol. Chem., March 28, 1997; 272(13): 8739 - 8743.
[Abstract] [Full Text] [PDF]


Home page
DevelopmentHome page
M Sundaram, J Yochem, and M Han
A Ras-mediated signal transduction pathway is involved in the control of sex myoblast migration in Caenorhabditis elegans
Development, January 9, 1996; 122(9): 2823 - 2833.
[Abstract] [PDF]


Home page
DevelopmentHome page
R Hoskins, A. Hajnal, S. Harp, and S. Kim
The C. elegans vulval induction gene lin-2 encodes a member of the MAGUK family of cell junction proteins
Development, January 1, 1996; 122(1): 97 - 111.
[Abstract] [PDF]


Home page
Genes Dev.Home page
G J Beitel, S Tuck, I Greenwald, and H R Horvitz
The Caenorhabditis elegans gene lin-1 encodes an ETS-domain protein and defines a branch of the vulval induction pathway.
Genes & Dev., December 15, 1995; 9(24): 3149 - 3162.
[Abstract] [PDF]


Home page
Genes Dev.Home page
N Singh and M Han
sur-2, a novel gene, functions late in the let-60 ras-mediated signaling pathway during Caenorhabditis elegans vulval induction.
Genes & Dev., September 15, 1995; 9(18): 2251 - 2265.
[Abstract] [PDF]


Home page
ScienceHome page
C. Yoon, J Lee, G. Jongeward, and P. Sternberg
Similarity of sli-1, a regulator of vulval development in C. elegans, to the mammalian proto-oncogene c-cbl
Science, August 25, 1995; 269(5227): 1102 - 1105.
[Abstract] [PDF]


Home page
Genes Dev.Home page
Y Wu, M Han, and K L Guan
MEK-2, a Caenorhabditis elegans MAP kinase kinase, functions in Ras-mediated vulval induction and other developmental events.
Genes & Dev., March 15, 1995; 9(6): 742 - 755.
[Abstract] [PDF]


Home page
Genes Dev.Home page
K Kornfeld, K L Guan, and H R Horvitz
The Caenorhabditis elegans gene mek-2 is required for vulval induction and encodes a protein similar to the protein kinase MEK.
Genes & Dev., March 15, 1995; 9(6): 756 - 768.
[Abstract] [PDF]


Home page
Genes Dev.Home page
S Tuck and I Greenwald
lin-25, a gene required for vulval induction in Caenorhabditis elegans.
Genes & Dev., February 1, 1995; 9(3): 341 - 357.
[Abstract] [PDF]


Home page
DevelopmentHome page
D. Church, K. Guan, and E. Lambie
Three genes of the MAP kinase cascade, mek-2, mpk-1/sur-1 and let-60 ras, are required for meiotic cell cycle progression in Caenorhabditis elegans
Development, January 8, 1995; 121(8): 2525 - 2535.
[Abstract] [PDF]


Home page
DevelopmentHome page
M Koga and Y Ohshima
Mosaic analysis of the let-23 gene function in vulval induction of Caenorhabditis elegans
Development, January 8, 1995; 121(8): 2655 - 2666.
[Abstract] [PDF]


Home page
DevelopmentHome page
A. Newman, J. White, and P. Sternberg
The Caenorhabditis elegans lin-12 gene mediates induction of ventral uterine specialization by the anchor cell
Development, January 2, 1995; 121(2): 263 - 271.
[Abstract] [PDF]


Home page
Genes Dev.Home page
M R Lackner, K Kornfeld, L M Miller, H R Horvitz, and S K Kim
A MAP kinase homolog, mpk-1, is involved in ras-mediated induction of vulval cell fates in Caenorhabditis elegans.
Genes & Dev., January 15, 1994; 8(2): 160 - 173.
[Abstract] [PDF]


Home page
DevelopmentHome page
H. Chamberlin and P. Sternberg
The lin-3/let-23 pathway mediates inductive signalling during male spicule development in Caenorhabditis elegans
Development, January 10, 1994; 120(10): 2713 - 2721.
[Abstract] [PDF]


Home page
DevelopmentHome page
J Austin and C Kenyon
Cell contact regulates neuroblast formation in the Caenorhabditis elegans lateral epidermis
Development, January 2, 1994; 120(2): 313 - 323.
[Abstract] [PDF]


Home page
Cold Spring Harb Symp Quant BiolHome page
P.W. Sternberg, C.H. Yoon, J. Lee, G.D. Jongeward, P.S. Kayne, W.S. Katz, G. Lesa, J. Liu, A. Golden, L.S. Huang, et al.
Molecular Genetics of Proto-oncogenes and Candidate Tumor Suppressors in Caenorhabditis elegans
Cold Spring Harb Symp Quant Biol, January 1, 1994; 59(0): 155 - 163.
[Abstract] [PDF]


Home page
Genes Dev.Home page
J Lee, G D Jongeward, and P W Sternberg
unc-101, a gene required for many aspects of Caenorhabditis elegans development and behavior, encodes a clathrin-associated protein.
Genes & Dev., January 1, 1994; 8(1): 60 - 73.
[Abstract] [PDF]


Home page
Genes Dev.Home page
L M Miller, M E Gallegos, B A Morisseau, and S K Kim
lin-31, a Caenorhabditis elegans HNF-3/fork head transcription factor homolog, specifies three alternative cell fates in vulval development.
Genes & Dev., June 1, 1993; 7(6): 933 - 947.
[Abstract] [PDF]


Home page
ScienceHome page
L Bonfini, C. Karlovich, C Dasgupta, and U Banerjee
The Son of sevenless gene product: a putative activator of Ras
Science, January 31, 1992; 255(5044): 603 - 606.
[Abstract] [PDF]


Home page
Cold Spring Harb Symp Quant BiolHome page
P.W. Sternberg, R.J. Hill, G. Jongeward, L.S. Huang, and L. Carta
Intercellular Signaling during Caenorhabditis elegans Vulval Induction
Cold Spring Harb Symp Quant Biol, January 1, 1992; 57(0): 353 - 362.
[Abstract] [PDF]


Home page
Cold Spring Harb Symp Quant BiolHome page
S.G. Clark, M.J. Stern, and H.R. Horvitz
Genes Involved in Two Caenorhabditis elegans Cell-signaling Pathways
Cold Spring Harb Symp Quant Biol, January 1, 1992; 57(0): 363 - 373.
[Abstract] [PDF]


Home page
Genes Dev.Home page
M Han and P W Sternberg
Analysis of dominant-negative mutations of the Caenorhabditis elegans let-60 ras gene.
Genes & Dev., December 1, 1991; 5(12a): 2188 - 2198.
[Abstract] [PDF]


Home page
J. Biol. Chem.Home page
C. M. Crowder, E. J. Westover, A. S. Kumar, R. E. Ostlund Jr., and D. F. Covey
Enantiospecificity of Cholesterol Function in Vivo
J. Biol. Chem., November 21, 2001; 276(48): 44369 - 44372.
[Abstract] [Full Text] [PDF]