The cell adhesion molecule Echinoid promotes tissue survival and separately restricts tissue overgrowth inDrosophilaimaginal discs

Abstract

The interactions that cells inDrosophilaimaginal discs have with their neighbors are known to regulate their ability to survive. In a screen of genes encoding cell surface proteins for gene knockdowns that affect the size or shape of mutant clones, we found that clones of cells with reduced levels ofechinoid(ed) are fewer, smaller, and can be eliminated during development. In contrast, discs composed mostly ofedmutant tissue are overgrown. We find thatedmutant tissue has lower levels of the anti-apoptotic protein Diap1 and has increased levels of apoptosis which is consistent with the observed underrepresentation ofedmutant clones and the slow growth ofedmutant tissue. The eventual overgrowth ofedmutant tissue results not from accelerated growth, but from prolonged growth resulting from a failure to arrest growth at the appropriate final size. Ed has previously been shown to physically interact with multiple Hippo-pathway components and it has been proposed to promote Hippo pathway signaling, to exclude Yorkie (Yki) from the nucleus, and restrain the expression of Yki-target genes. We did not observe changes in Yki localization inedmutant tissue and found decreased levels of expression of several Yorkie-target genes, findings inconsistent with the proposed effect of Ed on Yki. We did, however, observe increased expression of several Yki-target genes in wild-type cells neighboringedmutant cells, which may contribute to elimination ofedmutant clones. Thus,edhas two distinct functions: an anti-apoptotic function by maintaining Diap1 levels, and a function to arrest growth at the appropriate final size. Both of these are unlikely to be explained by a simple effect on the Hippo pathway.