NCBP2 modulates neurodevelopmental defects of the 3q29 deletion in Drosophila and X. laevis models

The chromosome 3q29 deletion is associated with a range of neurodevelopmental disorders. Here, we used quantitative methods to assay Drosophila melanogaster and Xenopus laevis models with tissue-specific knockdown of individual homologs of genes within the 3q29 region. We identified developmental, cellular and neuronal phenotypes for multiple homologs, potentially due to altered apoptosis and cell cycle mechanisms. We screened for 314 pairwise knockdowns of fly homologs of 3q29 genes, and identified 44 interactions between pairs of homologs and 34 interactions with other neurodevelopmental genes. NCBP2 homologs in Drosophila (Cbp20) and X. laevis (ncbp2) enhanced the phenotypes of the other homologs, leading to significant increases in apoptosis that disrupted cellular organization and brain morphology. These cellular and neuronal defects were rescued with overexpression of the apoptosis inhibitors Diap1 and xiap in both models. Our study suggests that NCBP2-mediated genetic interactions contribute to the neurodevelopmental features of the 3q29 deletion.