More avast! For dorsal closure: Characterization of acal and its relation with Drosophila Jun N-terminal kinase signaling

Abstract

Jun N-terminal kinase (JNK) signaling regulates epithelial remodeling throughout metazoa. Drosophila melanogaster possesses only one homolog of JNK, Basket, which coordinates dorsal closure during embryonic development. During dorsal closure the lateral epidermis changes shape and stretches over the amnioserosa towards the midline, wrapping up the embryo dorsally. Mutant embryos for basket and other members of the pathway die due to failures in closure, leaving dorsal and anterior holes in cuticle preparations. In this work, we describe an uncharacterized gene whose mutants show dorsal closure defects in cuticle preparations. We also describe its relationship with Basket signaling. The locus, acal, is conserved among drosophilids at the nucleotide level, but the transcripts only have small open reading frames that are not conserved. We hypothesize they are non-coding RNA genes. acal is enriched in the nuclear fraction, and is expressed in the epidermis during dorsal closure. By genetic interactions with basket mutants, we observed that it negatively regulates Basket signaling. This was confirmed by expression of puckered-lacZ, a reporter for Basket signaling activity. Finally, to get further insight into acal, we performed genetic interactions with known inhibitors of Basket signaling. From these assays, we believe that Acal acts in conjunction with Raw and independently of Hindsight, both of which inhibit Basket signaling in the epidermis and in the amnioserosa, respectively. Work is now focused on determining the molecular function of acal and its mechanism of inhibition.