Critical roles of <i>Drosophila</i> ubiquitin carboxyl-terminal hydrolase in eye development

Ubiquitin C-terminal hydrolase L1 (UCH-L1) is a protein in the ubiquitin-proteasome system involved in numerous cellular processes and implicated in various human diseases, including cancer, neurodegenerative diseases, and metabolic syndrome. However, its roles in development remain poorly understood. In this study, we used <i>Drosophila melanogaster</i> as a model to investigate the function of UCH-L1. The <i>Drosophila</i> homolog of <i>UCH-L1</i>, <i>Uch</i>, was specifically knocked down in the eye imaginal disk using RNA interference (RNAi). The results showed that loss of Uch function induced a rough eye phenotype characterized by abnormal ommatidia, including disorganized arrangement, variable sizes, and irregular orientations. In addition, Uch knockdown significantly affected cone cells, photoreceptor cells, and pigment cells. Remarkably, these defects were fully rescued when <i>rho-1</i>, a protease that releases the Spitz, the ligand of EGFR signaling, was co-knocked down. Taken together, these findings strongly demonstrated that Uch plays a crucial role in the development of various <i>Drosophila</i> eye cell types and functions in coordination with rhomboid-1 in the <i>Drosophila</i> EGFR signaling pathway.