Intron-targeted mutagenesis reveals roles for Dscam1 RNA pairing architecture-driven splicing bias in neuronal wiring

• DOI: 10.1016/j.celrep.2021.109373
• Publication Date: 2021-07-13T15:08:54Z
• Authors: Weiling Hong; Jian Zhang; Haiyang Dong; Yang Shi; Hongru Ma; Fengyan Zhou; Bingbing Xu; Ying Fu; Shixin Zhang; Shouqing Hou; Guo Li; Yandan Wu; Shuo Chen; Xiaohua Zhu; Wendong You; Feng Shi; Xiaofeng Yang; Zhefeng Gong; Jianhua Huang; Yongfeng Jin
• Keywords: Male; QH301-705.5; self-avoidance; alternative splicing; 03 medical and health sciences; Protein Domains; Animals; Drosophila Proteins; Protein Isoforms; Biology (General); Base Pairing; Alleles; Mushroom Bodies; Neurons; 0303 health sciences; Base Sequence; Dendrites; Exons; neuronal wiring; Axons; Introns; isoform diversity; Drosophila melanogaster; Phenotype; Mutagenesis; Dscam; splicing bias; RNA; Female; Cell Adhesion Molecules

Drosophila melanogaster Down syndrome cell adhesion molecule (Dscam1) can generate 38,016 different isoforms through largely stochastic, yet highly biased, alternative splicing. These are required for nervous functions. However, the functional significance of splicing bias remains unknown. Here, we provide evidence that Dscam1 is mushroom body (MB) axonal wiring. We mutant flies with normal overall protein levels and an identical number but global changes in exon 4 9 isoform (DscamΔ4D-/- DscamΔ9D-/-), respectively. In contrast to DscamΔ4D-/-, DscamΔ9D-/- exhibits remarkable MB defects, suggesting a variable domain-specific requirement bias. Importantly, cause defects do not influence self-avoidance branches. conclude that, provides molecular basis neurite self-avoidance, may play role wiring by influencing non-repulsive signaling.