The Drosophila homologue of MEGF8 is essential for early development.

Sci Rep 2018 06 8;8(1):8790. Epub 2018 Jun 8.

MRC Weatherall Institute of Molecular Medicine, Radcliffe Department of Medicine, University of Oxford, Oxford, OX3 9DS, UK.

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 or 3 instar larvae. Larvae were delayed in transition to 3 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.

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http://www.nature.com/articles/s41598-018-27076-y
Publisher Site
http://dx.doi.org/10.1038/s41598-018-27076-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5993795PMC
June 2018
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References

(Supplied by CrossRef)

G Carpenter et al.
Rep Soc Study Dis Child L. 1901

D Jenkins et al.
Am. J. Hum. Genet. 2007

SRF Twigg et al.
Am. J. Hum. Genet. 2012

JD Overton et al.
J. Biol. Chem. 2011

CN Aune et al.
Pediatr. Res. 2008

C Engelhard et al.
Elife 2013

Z Zhang et al.
PNAS 2009

K Fuller et al.
Dev. Biol. 2014

M Fliegauf et al.
Nat. Rev. Mol. Cell Biol. 2007

J-B Coutelis et al.
EMBO Rep. 2014

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