# UCH-L1 regulates eye differentiation-related genes and modulates EGFR signalling in Drosophila melanogaster

## TL;DR

This study shows that UCH-L1 in fruit flies affects eye development by regulating genes and signaling pathways important for photoreceptor cell differentiation.

## Contribution

The study reveals a novel role for dUCH in regulating EGFR signaling and eye differentiation genes in Drosophila.

## Key findings

- dUCH knockdown reduces EGFR protein levels and downregulates Spitz and Draf in the MAPK pathway.
- Loss of dUCH affects eye cell differentiation genes like sens, salm, lz, barth1/2, and sev.
- dUCH is involved in R7 photoreceptor differentiation by regulating pros, lz, barth1/2, and sev.

## Abstract

UCH-L1 (Ubiquitin Carboxyl-terminal Hydrolase – L1) is a protein that plays a critical role in the ubiquitin-proteasome system. Previous studies have demonstrated a link between UCH-L1 and various diseases, including neurodegenerative disorders, diabetes, and cancer. However, the role of UCH-L1 in development remains unclear. To investigate the functions of UCH-L1 in a living organism, taking advantage of the Drosophila model, and to explore the correlation between Drosophila UCH (dUCH) and human UCH-L1, we established a GAL4/UAS-targeted expression system to examine the effect of dUCH on Drosophila eye development. We found that knockdown of dUCH resulted in a rough eye phenotype associated with the MAPK pathway. In this study, for the first time, we revealed that loss of dUCH function leads to a reduction in EGFR protein levels. Additionally, dUCH knockdown downregulated Spitz (spi), a ligand of EGFR, as well as Draf, a key component of the MAPK pathway. Furthermore, under dUCH knockdown conditions, several genes known to play critical roles in eye cell differentiation were affected, including the downregulation of sens, salm, lz, barth1/2, and salm, which are essential for the differentiation of R2/5, R3/4, and R1/6 photoreceptor cells. Interestingly, dUCH was found to be involved not only in the MAPK pathway but also in the regulation of pros, lz, barth1/2, and sev gene expression, suggesting its role in R7 photoreceptor differentiation. Taken together, these findings highlight the important role of dUCH in regulating genes associated with eye cell differentiation and its involvement in EGFR signalling in Drosophila melanogaster.