Abstract:
During organogenesis, cell proliferation is followed by the differentiation of specific
cell types to form an organ. Any aberration in differentiation can result in develop-
mental defects, which can result in a partial to a near-complete loss of an organ. We
employ the Drosophila eye model to understand the genetic and molecular mecha-
nisms involved in the process of differentiation. In a forward genetic screen, we iden-
tified, cullin-4 (cul-4 ), which encodes an E3 ubiquitin ligase, to play an important role
in retinal differentiation. During development, cul-4 is known to be involved in pro-
tein degradation, regulation of genomic stability, and regulation of cell cycle. Previ-
ously, we have reported that cul-4 regulates cell death during eye development by
downregulating Wingless (Wg)/Wnt signaling pathway. We found that loss-of-
function of cul-4 results in a reduced eye phenotype, which can be due to onset of
cell death. However, we found that loss-of-function of cul-4 also affects retinal
development by downregulating retinal determination (RD) gene expression. Early
markers of retinal differentiation are dysregulated in cul-4 loss of function conditions,
indicating that cul-4 is necessary for differentiation.