Control of DAF-7 TGF-(alpha) expression and neuronal process development by a receptor tyrosine kinase KIN-8 in Caenorhabditis elegans.
KIN-8 in C. elegans is highly homologous to human ROR-1 and 2 receptor tyrosine kinases of unknown functions. These kinases belong to a new subfamily related to the Trk subfamily. A kin-8 promoter::gfp fusion gene was expressed in ASI and many other neurons as well as in pharyngeal and head muscles. A kin-8 deletion mutant was isolated and showed constitutive dauer larva formation (Daf-c) phenotype: about half of the F(1) progeny became dauer larvae when they were cultivated on an old lawn of E. coli as food. Among the cells expressing kin-8::gfp, only ASI sensory neurons are known to express DAF-7 TGF-(beta), a key molecule preventing dauer larva formation. In the kin-8 deletion mutant, expression of daf-7::gfp in ASI was greatly reduced, dye-filling in ASI was specifically lost and ASI sensory processes did not completely extend into the amphid pore. The Daf-c phenotype was suppressed by daf-7 cDNA expression or a daf-3 null mutation. ASI-directed expression of kin-8 cDNA under the daf-7 promoter or expression by a heat shock promoter rescued the dye-filling defect, but not the Daf-c phenotype, of the kin-8 mutant. These results show that the kin-8 mutation causes the Daf-c phenotype through reduction of the daf-7 gene expression and that KIN-8 function is cell-autonomous for the dye-filling in ASI. KIN-8 is required for the process development of ASI, and also involved in promotion of daf-7 expression through a physiological or developmental function.
Koga
M
M
Department of Biology, Graduate School of Sciences, Kyushu University, Fukuoka, Japan.
Take-uchi
M
M
Tameishi
T
T
Ohshima
Y
Y
D000595:Amino Acid Sequence; D000818:Animals; D030801:Animals, Genetically Modified; D001824:Body Constitution / Q000235:genetics; D001921:Brain / Q000002:abnormalities; D017173:Caenorhabditis elegans / Q000235:genetics / Q000254:growth & development*; D029742:Caenorhabditis elegans Proteins; D003001:Cloning, Molecular; D018076:DNA, Complementary; D017353:Gene Deletion; D018507:Gene Expression Regulation, Developmental; D006066:Gonads / Q000002:abnormalities; D049452:Green Fluorescent Proteins; D006360:Heat-Shock Proteins / Q000235:genetics; D015801:Helminth Proteins / Q000235:genetics* / Q000378:metabolism; D006801:Humans; D007814:Larva / Q000502:physiology; D008164:Luminescent Proteins / Q000235:genetics; D008969:Molecular Sequence Data; D009154:Mutation; D009475:Neurons, Afferent / Q000502:physiology*; D011401:Promoter Regions, Genetic; D020794:Receptor Protein-Tyrosine Kinases / Q000235:genetics* / Q000378:metabolism*; D057050:Receptor Tyrosine Kinase-like Orphan Receptors; D017386:Sequence Homology, Amino Acid; D016212:Transforming Growth Factor beta / Q000235:genetics* / Q000378:metabolism
D029742:Caenorhabditis elegans Proteins; C102095:DAF-7 protein, C elegans; D018076:DNA, Complementary; D006360:Heat-Shock Proteins; D015801:Helminth Proteins; D008164:Luminescent Proteins; D016212:Transforming Growth Factor beta; D049452:Green Fluorescent Proteins; C526267:CAM-1 protein, C elegans; D020794:Receptor Protein-Tyrosine Kinases; D057050:Receptor Tyrosine Kinase-like Orphan Receptors