The Drosophila homologue of MEGF8 is essential for early development

Mutations of the gene MEGF8 cause Carpenter syndrome in humans, and the mouse orthologue has been functionally associated with Nodal and Bmp4 signalling. Here, we have investigated the phenotype associated with loss-of-function of CG7466 , a gene that encodes the Drosophila homologue of MEGF8 . We generated three different frame-shift null mutations in CG7466 using CRISPR/Cas9 gene editing. Heterozygous flies appeared normal, but homozygous animals had disorganised denticle belts and died as 2 nd or 3 rd instar larvae. Larvae were delayed in transition to 3 rd instars and showed arrested growth, which was associated with abnormal feeding behaviour and prolonged survival when yeast food was supplemented with sucrose. RNAi-mediated knockdown using the Gal4 - UAS system resulted in lethality with ubiquitous and tissue-specific Gal4 drivers, and growth defects including abnormal bristle number and orientation in a subset of escapers. We conclude that CG7466 is essential for larval development and that diminished function perturbs denticle and bristle formation.