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

Abstract

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.

Tuned polymerization of the transcription factor Yan limits off-DNA sequestration to confer context-specific repression

“…To image adult eyes, decapitated heads were imaged with a Canon EOS Rebel camera fitted to a Leica dissecting microscope. Adult eye histology and sectioning was performed as described previously ( Davis et al, 2017 ), except that embedded heads were incubated in 100% resin for 24 hr at room temperature.…”

The Eyes Absent Proteins: Unusual HAD Family Tyrosine Phosphatases

“…Curiously, while the PTP activity of the Drosophila Eya proteins was initially implicated in eye formation using GAL4-UAS mediated genetic rescue experiments [ 9 , 25 ], subsequent studies using genomic rescue showed that the tyrosine phosphatase activity was dispensable for fly eye formation and survival [ 26 ]. The emerging theme in Drosophila appears to be that, while the Eya PTP activity contributes to development, it is not essential [ 27 ]. A recent study suggests that fly Eya PTP activity contributes to the “robustness” of the retinal determination gene network; heterozygosity for other components of this network ( sine oculis or dachshund ) compromised the ability of PTP-dead Eya to rescue retinal defects [ 27 ].…”

The Eya1 Phosphatase Mediates Shh-Driven Symmetric Cell Division of Cerebellar Granule Cell Precursors

“…In previous studies, we found that Eya1 phosphatase activity is essential to promote Shh signaling [19]. While several other studies also suggest that phosphatase activity contributes to Eya-dependent transcriptional output [38], data from the Drosophila system suggest that phosphatase activity of the Eya family members may be dispensable for some of its actions [39-41]. Thus far, four physiological substrates of Eya phosphatase activity have been identified: the histone H2A variant H2AX [42, 43], the estrogen receptor ERβ [44], the proto-oncogene Myc [45] and Notch1 [46], and additional potential substrates have been suggested [34, 47, 48].…”