Mutations that impair Eyes absent tyrosine phosphatase activity in vitro reduce robustness of retinal determination gene network output in Drosophila

• Published in: PloS one Vol. 12; no. 11; p. e0187546
• Main Authors: Davis, Trevor L, Hoi, Charlene S L, Rebay, Ilaria
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 06.11.2017; Public Library of Science (PLoS)
• Subjects: Animals; Biology; Biology and Life Sciences; Cancer; Cellular communication; Drosophila; Drosophila Proteins - genetics; Drosophila Proteins - metabolism; Eye (anatomy); Eye Proteins - genetics; Eye Proteins - metabolism; Females; Fertility; Gene mutation; Gene Regulatory Networks; Genes; Genetic aspects; Genetics; Genomics; Heterozygosity; Heterozygote; Insects; Kinases; Medical research; Medicine and Health Sciences; Modularity; Mutation; Phosphatase; Phosphatases; Physical Sciences; Production management; Protein Tyrosine Phosphatases - genetics; Protein Tyrosine Phosphatases - metabolism; Protein-tyrosine-phosphatase; Proteins; Research and Analysis Methods; Retina; Retina - growth & development; Retina - metabolism; Robustness; Signaling; Stem cells; Threonine; Threonine phosphatase; Transcription; Transcription factors; Transgenes; Tyrosine; Viability; United States > US; Illinois; Chicago Illinois
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0187546

A limited collection of signaling networks and transcriptional effectors directs the full spectrum of cellular behaviors that comprise development. One mechanism to diversify regulatory potential is to combine multiple biochemical activities into the same protein. Exemplifying this principle of modularity, Eyes absent (Eya), originally identified as a transcriptional co-activator within the retinal determination gene network (RDGN), also harbors tyrosine and threonine phosphatase activities. Although mounting evidence argues for the importance of Eya's phosphatase activities to mammalian biology, genetic rescue experiments in Drosophila have shown that the tyrosine phosphatase function is dispensable for normal development. In this study, we repeated these rescue experiments in genetically sensitized backgrounds in which the dose of one or more RDGN factor was reduced. Heterozygosity for sine oculis or dachshund, both core RDGN members, compromised the ability of phosphatase-dead eya, but not of the control wild type eya transgene, to rescue the retinal defects and reduced viability associated with eya loss. We speculate that Eya's tyrosine phosphatase activity, although non-essential, confers robustness to RDGN output.