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内容記述 |
He has identified a new member of the TGF-β superfamily, CET-1, from Caenorhabditis elegans. cet-1::GFP fusion is expressed in the ventral nerve cord and other neurons. He isolated cet-1 null mutant by Tc1 deletion method. cet-1 nullmutants have shortened bodies and male tail abnormal phenotype resembling sma mutants. These results suggest that cet-1, sma-2, sma-3, and sma-4 share a common pathway. Overexpression experiments demonstrated that cet-1 function requires wild type sma genes. Interestingly, CET-1 appears to affect body length in a dose dependent manner. Heterozygotes for cet-1 displayed body lengths ranging between null mutant and wild type, and overexpression of CET-1 in wild type worms elongated body length close to Jon mutants. Furthermore, his results show that cet-1 controls body length not proportionally but in two particular regions of the worm probably by changing cell volume. Moreover, genetic interaction of the cet-1 with mutants of the other TGF- β pathway in C. elegans, daf demonstrated that cet-1 is also involved at least partly in the daf signaling pathway. In male sensory ray patterning, lack of cet-1 function results in ray fusions. Epistasis analysis revealed that mab-21 lies downstream and is negatively regulated by the cet-1/sma pathway in the male tail. His results show that cet-1 controls diversed biological processes during C. elegans development probably through different target genes.<br /> He also has identified two genes, CeBRAM-1A and CeBRAM-2B, which are similar to human BRAM-1 previously identified as a BMP receptor associated molecule, in C. elegans. The C. elegans BRAMs (CeBRAM-1A and CeBRAM-2B) show significant amino acid identity with human BRAM-1, particularly in the C-terminal region. CeBRAM-1A was found to associate with DAF-1, the type I receptor in the daf pathway in C elegans as well as a vertebrate BMP type I receptor BMPRIA. CeBRAM-1A::GFP fusion protein is expressed mainly in amphid neurons such as ASK, ASH, and ASG etc, where DAF-1 is expressed. Loss-of-function of CeBRAM-1A gene showed that the mutant worms looked normal except that they showed a behavior of head-lifting phenotype. Genetic interaction of CeBRAM-1A with previously known daf-7 TGF-β pathway mutants revealed that CeBRAM-1A negatively regulates the daf-7 TGF-β pathway and functions between daf-1 type I receptor and daf-14 SMAD. On the other hand, CeBRAM-2B::GFP fusion protein was expressed strongly in pharyngeal muscle and intestinal cells. This expression pattern of CeBRAM-2B is similar to that of sma-6 type I receptor of the cet-1/sma pathway. Interestingly, double strand RNA interference (dsRNAi) of CeBR,AM-2B showed Lon phenotype. These results strongly suggest that CeBRAM-1A and CeBRAM-2B may function as negative regulators of two distinct TGF-β signal pathways, the daf pathway and the sma pathway respectively in C. elegans. Thus, he proposes that CeBRAM-1A and CeBRAM-2B define a novel class of molecules that serve as a negative regulator of TGF- f3 pathways acting downstream of the type I receptor. |
要旨・審査要旨 / Abstract, Screening Result (268.2 kB)
