Transcription factor choice in the Hippo signaling pathway: homothorax and yorkie regulation of the microRNA bantam in the progenitor domain of the Drosophila eye imaginal disc

Abstract

The accurate control of cell proliferation and survival is critical for animal development. The Hippo tumor suppressor pathway regulates both of these parameters by controlling the nuclear availability of the transcriptional coactivator Yorkie (Yki), which regulates downstream target genes together with Scalloped (Sd), a DNA-binding protein. Here we provide evidence that Yki can also regulate target genes in conjunction with Homothorax (Hth) and Teashirt (Tsh), two DNA-binding transcription factors expressed in the uncommitted progenitor cells of the Drosophila eye imaginal disc. Clonal analyses demonstrate that Hth and Tsh promote cell proliferation and protect eye progenitor cells from apoptosis. Genetic epistasis experiments suggest that Hth and Tsh execute these functions with Yki, in part by up-regulating the microRNA bantam. A physical interaction between Hth and Yki can be detected in cell culture, and we show that Hth and Yki are bound to a DNA sequence ;14 kb upstream of the bantam hairpin in eye imaginal disc cells, arguing that this regulation is direct. These data suggest that the Hippo pathway uses different DNA-binding transcription factors depending on the cellular context. In the eye disc, Hth and Tsh provide spatial information to this pathway, promoting cell proliferation and survival in the progenitor domain.[Keywords: Drosophila eye development; Hippo signaling pathway; Homothorax; Yorkie; apoptosis; cell proliferation] Supplemental material is available at http://www.genesdev.org.

Wbp2 cooperates with Yorkie to drive tissue growth downstream of the Salvador–Warts–Hippo pathway

“…Several transcription factors have been shown to control tissue growth in conjunction with Yki but how these proteins regulate transcription is still unclear. [15][16][17][18] What is better defined is the mechanism by which Yki activity is regulated by the SWH pathway; Wts/LATS1/2-mediated phosphorylation of Yki/YAP results in 14-3-3-dependent cytoplasmic sequestration of Yki/YAP, thus preventing Yki/ YAP activity in the nucleus. 3 To investigate whether Wbp2 affected Yki by influencing SWH pathway-mediated repression, we determined whether Wbp2 influenced Wts-dependent phosphorylation of Yki in S2 cells using anti-phospho-Yki-S168 antibody.…”

“…14 Yki drives a growth-regulatory transcriptional programme by regulating transcription factors that include Scalloped (Sd), [15][16][17] Homothorax (Hth) and Teashirt (Tsh). 18 Yki and YAP bind via a region of B100 amino acids in their N-termini to Sd and TEAD1-4, respectively. 15,19 Additional transcription factors have been shown to be activated by YAP including pEBP2a, ErbB-4 and p73, and these factors bind to the WW domains of YAP via PPxY (PY) motifs.…”

When pathways collide: collaboration and connivance among signalling proteins in development

“…The complexity of bantam control also highlights differential transcription factor interactions with Yorkie in growth control. While the TEAD family transcription factor Scalloped functions with Yorkie to regulate growth in the wing, recent studies have shown that the TALE family transcription factor Homothorax, together with the Zn finger transcription factor Teashirt, function with Yorkie to regulate growth in the fly eye disc 78 .…”

bantam microRNA is a negative regulator of the Drosophila decapentaplegic pathway

“…However, there is no evidence that Yki and ban function in a feedback loop [27,29]. In eye imaginal discs, Yki acts together with Homothorax (Hth) and Teashirt (Tsh), two DNA-binding transcription factors, upregulating ban to promote cell proliferation and survival in the progenitor domain [30]. Hth and Yki are bound to a DNA sequence ~ 14 kb upstream of the ban hairpin in eye imaginal disc cells by chromatin immunoprecipitation, suggesting that this regulation might be direct.…”