Forkhead as a cross-regulator of cell death and the innate immune response in the Malpighian tubules of Drosophila melanogaster

Abstract

Forkhead (fkh) transcription factor derives its name from the distinctive appearance of the DNA-binding motifs when attached to DNA. In mammals, they are grouped into seven families from FOXA to FOXS. FoxA subfamily participates in several essential functions, including the development of various organs, the regulation of senescence, proliferation, and metabolic homeostasis. In this study, we provide evidence that the Drosophila orthologue of FOXA, known as fkh, is instrumental in preventing programmed cell death in Drosophila Malpighian tubules (MTs) during metamorphosis. This characteristic is unique to Malpighian tubules when compared to several other larval tissues. We also demonstrate its role in the immune function of the MTs, as its depletion in MTs suppresses the expression of Anti-Microbial Peptides (AMPs). Furthermore, reduced expression of NF-kB transcription factor, Relish and Dorsal, could contribute to the reduced synthesis of AMPs. Fkh also regulates the fluid secretion of the MTs and its absence disrupts the ion transporters thus affecting fluid homeostasis. Our results demonstrate that fkh plays an essential role in the survival of MTs, without that the MTs cannot survive and fail to mount an effective immune response.