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C. elegans LIN-18 Is a Ryk Ortholog and Functions in Parallel to LIN-17/Frizzled in Wnt Signaling

Inoue, Takao and Oz, Helieh S. and Wiland, Debra and Gharib, Shahla and Deshpande, Rashmi and Hill, Russell J. and Katz, Wendy S. and Sternberg, Paul W. (2004) C. elegans LIN-18 Is a Ryk Ortholog and Functions in Parallel to LIN-17/Frizzled in Wnt Signaling. Cell, 118 (6). pp. 795-806. ISSN 0092-8674. doi:10.1016/j.cell.2004.09.001.

[img] PDF (Supplemental Figure S1. Sequence Alignment of C. elegans and C. briggsae LIN-18, Derailed, Doughnut, and Human Ryk) - Supplemental Material
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Wnt proteins are intercellular signals that regulate various aspects of animal development. In Caenorhabditis elegans, mutations in lin-17, a Frizzled-class Wnt receptor, and in lin-18 affect cell fate patterning in the P7.p vulval lineage. We found that lin-18 encodes a member of the Ryk/Derailed family of tyrosine kinase-related receptors, recently found to function as Wnt receptors. Members of this family have nonactive kinase domains. The LIN-18 kinase domain is dispensable for LIN-18 function, while the Wnt binding WIF domain is required. We also found that Wnt proteins LIN-44, MOM-2, and CWN-2 redundantly regulate P7.p patterning. Genetic interactions indicate that LIN-17 and LIN-18 function independently of each other in parallel pathways, and different ligands display different receptor specificities. Thus, two independent Wnt signaling pathways, one employing a Ryk receptor and the other a Frizzled receptor, function in parallel to regulate cell fate patterning in the C. elegans vulva.

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Sternberg, Paul W.0000-0002-7699-0173
Additional Information:© 2004 Cell Press. Received 16 March 2004, Revised 14 July 2004, Accepted 24 July 2004, Available online 16 September 2004. Published: September 16, 2004. We thank J. Goodwin for technical assistance, X.Z.S. Xu for DsRed2 plasmids, and B.P. Gupta for lin-17 plasmids. We thank A. Fire, S. Xu, J. Ahnn, and G. Seydoux for gfp vectors, D. Eisenmann and S. Kim for ga75, and Y. Kohara for cDNA clones and in situ data. Some strains were obtained from Caenorhabditis Genetics Center, funded by NIH, National Center for Research Resources. P.W.S. is an Investigator with and W.S.K. was an Associate with the HHMI, which supported this work. T.I. was supported by fellowship DRG-1646 from the Damon Runyon Cancer Research Foundation. W.S.K. was also supported by grants: March of Dimes 5-FY97-0674, ACS IRG-163H, and EPSCoR OSR-9452895. R.J.H. was supported by March of Dimes 5-FY00-550.
Funding AgencyGrant Number
Howard Hughes Medical Institute (HHMI)UNSPECIFIED
Damon Runyon Cancer Research FoundationDRG-1646
March of Dimes5-FY97-0674
American Cancer SocietyIRG-163H
March of Dimes5-FY00-550
Issue or Number:6
Record Number:CaltechAUTHORS:20170408-160853586
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Official Citation:Takao Inoue, Helieh S. Oz, Debra Wiland, Shahla Gharib, Rashmi Deshpande, Russell J. Hill, Wendy S. Katz, Paul W. Sternberg, C. elegans LIN-18 Is a Ryk Ortholog and Functions in Parallel to LIN-17/Frizzled in Wnt Signaling, Cell, Volume 118, Issue 6, 17 September 2004, Pages 795-806, ISSN 0092-8674, (
Usage Policy:No commercial reproduction, distribution, display or performance rights in this work are provided.
ID Code:76137
Deposited By: 1Science Import
Deposited On:22 Jun 2017 21:15
Last Modified:15 Nov 2021 16:57

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