despite the presence of additional phosphorylated RTKs

In line with AZD3514 this prediction, when Tsh was expressed ectopically in posterior margin cells, clones and peripodial cells might be induced to overgrow. On the other hand, Tsh clones posterior to the MF in the main epithelium did not over develop and as an alternative classified into photoreceptor clus ters with apparently normal morphology. Hence, there is strong correlation between Tsh and Hth coex pression and their ability to produce overgrowths. Consis tently, when both Tsh and Hth are coexpressed in clones, they overgrow wherever they occur in the eye disc. As one more test to test whether Hth and Tsh are both necessary to stimulate overgrowths, mosaic analysis was used by us with repressible cell marker to generate hthP2 clones that simultaneously express Tsh. These Tsh, hthP2 clones never overgrow, no matter where they're located in the disk. These datstrongly support the idethat Tsh and Hth have to be coexpressed to stimulate proliferation. We next examined the effect of Hth Tsh expression on cell-cycle and differentiation Urogenital pelvic malignancy markers. The G2 cyclin Cyclin B is normally expressed in proliferating anterior progenitor cells and in row of cells posterior to the MF that refers to the second mitotic wave. In Hth Tsh clones posterior to the MF, CycB term is up-regulated. Similarly, staining for phosphory lated histone 3, marker for cells in mitosis, indicates that the cells in Hth Tsh clones are earnestly dividing. Ultimately, we examined Elav, marker for neural differentiation. In agreement with previous results showing the retinal dedication genes eyand so are repressed by Hth Tsh, Elais repressed in Hth Tsh expressing clones. These Marimastat results show that after Tsh and Hth are coexpressed in the eye disc, they promote proliferation and stop difference, mimicking the 2 main prop erties of anterior progenitor cells, which normally express these transcription factors, to gether. Hth Tsh function with the Hippo pathway In order to identify which pathways Hth and Tsh function with to advertise proliferation, we performed many genetic tests using mutations that both activate or in activate pathways previously implicated in growth con trol within the eye. We tested the Wg, Notch, and Jak Stat signaling trails, all implicated in muscle growth regu lation in Drosophila. With the exception of Wg, which will be necessary for hth expression in the progenitor domain, treatment of the pathways had no effect on hth or tsh expression. Moreover, none of the pathways were needed for ectopic Hth Tsh induced overgrowths. Based on these data, these three path ways are unlikely to mediate the proliferation and survival functions executed by Hth and Tsh in the anterior eye disc. In contrast to these results, we discovered that Tsh and Hth require components of the Hippo route to carry out their expansion inducing functions.