< i > NCBP2 < /i > modulates neurodevelopmental defects of the 3q29 deletion in < i > Drosophila < /i > and < i > Xenopus laevis < /i > models

by Mayanglambam Dhruba Singh, Matthew Jensen, Micaela Lasser, Emily Huber, Tanzeen Yusuff, Lucilla Pizzo, Brian Lifschutz, Inshya Desai, Alexis Kubina, Sneha Yennawar, Sydney Kim, Janani Iyer, Diego E. Rincon-Limas, Laura Anne Lowery, Santhosh Girirajan The 1.6 Mbp deletion on chromosome 3q29 is associated with a range of neurodevelopmental disorders, including schizophrenia, autism, microcephaly, and intellectual disability. Despite its importance towards neurodevelopment, the role of individual genes, genetic interactions, and disrupted biologi cal mechanisms underlying the deletion have not been thoroughly characterized. Here, we used quantitative methods to assayDrosophila melanogaster andXenopus laevis models with tissue-specific individual and pairwise knockdown of 14 homologs of genes within the 3q29 region. We identified developmental, cellular, and neuronal phenotypes for multiple homologs of 3q29 genes, potentially due to altered apoptosis and cell cycle mechanisms during development. Using the fly eye, we screened for 314 pairwise knockdowns of homologs of 3q29 genes and identified 44 interactions between pairs of homologs and 34 interactions with other neurodevelopmental genes. Interestingly,NCBP2 homologs inDrosophila (Cbp20) andX.laevis (ncbp2) enhanced the phenotypes of homologs of the other 3q29 genes, leading to significant increases in apoptosis that disrupted cellular organization and brain morphology. These cellular and neuronal defects were rescued with ...
Source: PLoS Genetics - Category: Genetics & Stem Cells Authors: Source Type: research