Non-canonical role of Yorkie in the development of Malpighian tubules of Drosophila melanogaster

Abstract

Tissue morphogenesis is a highly coordinated process necessary for correct morphology and function. The Hippo pathway plays a crucial role in regulating the size of organs, and mutation in this pathway can lead to the development of several diseases including tumor. Our study shows that transcriptional coactivator Yorkie, the downstream target of the Hippo pathway, plays a critical role in developing Malpighian tubules in Drosophila. The polycystic phenotype of Malpighian tubules, caused by the loss of the executioner caspase, Drice, results in enhanced expression of Yorkie. Consequently, the genetic reduction of Yorkie in Drice mutants can reduce the polycystic phenotype, reverting it to normal. Yorkie mutation restores actin organization in Drice mutant Malpighian tubules, leading to the proper cellular arrangement. Additionally, improvement in fluid secretion in the Malpighian tubules of Drice mutants was observed when Yorkie levels was reduced. Unexpectedly, Yorkie mutants have greatly elongated Malpighian tubules and its overexpression reduces the size. Collectively, our findings suggest that Yorkie has a non-canonical role in Malpighian tubule development and it genetically interacts with Drice to regulate the development of renal tubule. © 2025