yki is required for tissue growth and normal diap1 transcription. To further explore the role of Yki in Hpo signaling, a loss-of-function mutation of yki was generated by homologous recombination. The targeting construct was designed in such a way that all of the coding sequence of yki was replaced by the w+ marker, thus resulting in a null allele. yki null mutants are homozygous lethal and die as late embryos and early first instar larvae. A full-length yki cDNA driven by the ubiquitous α-tubulin promoter completely rescues yki null animals to viable and phenotypically normal adult flies (Huang, 2005).
eyeless-FLP was used to selectively remove yki function in over 90% of the eye disc cells. Eyes composed predominantly of yki mutant cells are markedly reduced in size when compared to control animals, thus revealing an essential function for yki in tissue growth. To follow yki mutant cells during development, FLP/FRT was used to examine genetically marked clones of yki mutant cells. yki mutant clones generated at 40 hr AED were hardly observed in third instar wing discs , with rare clones recovered containing only a few cells. yki mutant clones generated at a similar stage were more frequently recovered in the eye discs but contained much fewer cells than the wild-type twin spots. Despite the severe growth defects, loss of yki does not perturb early retina differentiation, as shown by the normal expression of the neuronal marker Elav. Taken together, these results reveal a specific requirement for yki in tissue growth (Huang, 2005).
To further probe the requirement of Yki in the Hpo pathway, diap1 transcription was examined in yki mutant clones using the thj5c8 diap1-lacZ reporter. Consistent with the overexpression results, diap1-lacZ expression is reduced in yki null cells in a cell-autonomous manner. Similar results were seen in the wing discs. DIAP1 protein level was also reduced in a cell-autonomous manner in yki mutant clones. Thus, yki is required for the normal level of diap1 transcription in Drosophila (Huang, 2005).
Reference names in red indicate recommended papers.
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Chan, E. H., et al. (2005). The Ste20-like kinase Mst2 activates the human large tumor suppressor kinase Lats1. Oncogene 24(12): 2076-86. 15688006
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Huang, J., Wu, S., Barrera, J., Matthews, K. and Pan, D. (2005). The Hippo signaling pathway coordinately regulates cell proliferation and apoptosis by inactivating Yorkie, the Drosophila homolog of YAP. Cell 122: 421-434. 16096061
Komuro, A., Nagai, M., Navin, N. E. and Sudol, M. (2003). WW domain-containing protein YAP associates with ErbB-4 and acts as a co-transcriptional activator for the carboxyl-terminal fragment of ErbB-4 that translocates to the nucleus. J. Biol. Chem. 278(35): 33334-41. 12807903
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Wu, S., Huang, J., Dong, J. and Pan, D. (2003). hippo encodes a Ste-20 family protein kinase that restricts cell proliferation and promotes apoptosis in conjunction with salvador and warts. Cell 114: 445-456. 12941273
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date revised: 20 May 2007
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