A systematic CRISPR screen reveals redundant and specific roles for Dscam1 isoform diversity in neuronal wiring.
Drosophila melanogaster Down syndrome cell adhesion molecule 1 (Dscam1) encodes 19,008 diverse ectodomain isoforms via the alternative splicing of exon 4, 6, and 9 clusters. However, whether individual isoforms or exon clusters have specific significance is unclear. Here, using phenotype-diversity c...
| Main Authors: | , , , , , , , , , , , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Public Library of Science (PLoS)
2023-07-01
|
| Series: | PLoS Biology |
| Online Access: | https://doi.org/10.1371/journal.pbio.3002197 |
| _version_ | 1797774513742544896 |
|---|---|
| author | Haiyang Dong Xi Yang Lili Wu Shixin Zhang Jian Zhang Pengjuan Guo Yiwen Du Changkun Pan Ying Fu Lei Li Jilong Shi Yanda Zhu Hongru Ma Lina Bian Bingbing Xu Guo Li Feng Shi Jianhua Huang Haihuai He Yongfeng Jin |
| author_facet | Haiyang Dong Xi Yang Lili Wu Shixin Zhang Jian Zhang Pengjuan Guo Yiwen Du Changkun Pan Ying Fu Lei Li Jilong Shi Yanda Zhu Hongru Ma Lina Bian Bingbing Xu Guo Li Feng Shi Jianhua Huang Haihuai He Yongfeng Jin |
| author_sort | Haiyang Dong |
| collection | DOAJ |
| description | Drosophila melanogaster Down syndrome cell adhesion molecule 1 (Dscam1) encodes 19,008 diverse ectodomain isoforms via the alternative splicing of exon 4, 6, and 9 clusters. However, whether individual isoforms or exon clusters have specific significance is unclear. Here, using phenotype-diversity correlation analysis, we reveal the redundant and specific roles of Dscam1 diversity in neuronal wiring. A series of deletion mutations were performed from the endogenous locus harboring exon 4, 6, or 9 clusters, reducing to 396 to 18,612 potential ectodomain isoforms. Of the 3 types of neurons assessed, dendrite self/non-self discrimination required a minimum number of isoforms (approximately 2,000), independent of exon clusters or isoforms. In contrast, normal axon patterning in the mushroom body and mechanosensory neurons requires many more isoforms that tend to associate with specific exon clusters or isoforms. We conclude that the role of the Dscam1 diversity in dendrite self/non-self discrimination is nonspecifically mediated by its isoform diversity. In contrast, a separate role requires variable domain- or isoform-related functions and is essential for other neurodevelopmental contexts, such as axonal growth and branching. Our findings shed new light on a general principle for the role of Dscam1 diversity in neuronal wiring. |
| first_indexed | 2024-03-12T22:22:12Z |
| format | Article |
| id | doaj.art-e1c82b623b464817a749cda1292d2502 |
| institution | Directory Open Access Journal |
| issn | 1544-9173 1545-7885 |
| language | English |
| last_indexed | 2024-03-12T22:22:12Z |
| publishDate | 2023-07-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS Biology |
| spelling | doaj.art-e1c82b623b464817a749cda1292d25022023-07-23T05:30:52ZengPublic Library of Science (PLoS)PLoS Biology1544-91731545-78852023-07-01217e300219710.1371/journal.pbio.3002197A systematic CRISPR screen reveals redundant and specific roles for Dscam1 isoform diversity in neuronal wiring.Haiyang DongXi YangLili WuShixin ZhangJian ZhangPengjuan GuoYiwen DuChangkun PanYing FuLei LiJilong ShiYanda ZhuHongru MaLina BianBingbing XuGuo LiFeng ShiJianhua HuangHaihuai HeYongfeng JinDrosophila melanogaster Down syndrome cell adhesion molecule 1 (Dscam1) encodes 19,008 diverse ectodomain isoforms via the alternative splicing of exon 4, 6, and 9 clusters. However, whether individual isoforms or exon clusters have specific significance is unclear. Here, using phenotype-diversity correlation analysis, we reveal the redundant and specific roles of Dscam1 diversity in neuronal wiring. A series of deletion mutations were performed from the endogenous locus harboring exon 4, 6, or 9 clusters, reducing to 396 to 18,612 potential ectodomain isoforms. Of the 3 types of neurons assessed, dendrite self/non-self discrimination required a minimum number of isoforms (approximately 2,000), independent of exon clusters or isoforms. In contrast, normal axon patterning in the mushroom body and mechanosensory neurons requires many more isoforms that tend to associate with specific exon clusters or isoforms. We conclude that the role of the Dscam1 diversity in dendrite self/non-self discrimination is nonspecifically mediated by its isoform diversity. In contrast, a separate role requires variable domain- or isoform-related functions and is essential for other neurodevelopmental contexts, such as axonal growth and branching. Our findings shed new light on a general principle for the role of Dscam1 diversity in neuronal wiring.https://doi.org/10.1371/journal.pbio.3002197 |
| spellingShingle | Haiyang Dong Xi Yang Lili Wu Shixin Zhang Jian Zhang Pengjuan Guo Yiwen Du Changkun Pan Ying Fu Lei Li Jilong Shi Yanda Zhu Hongru Ma Lina Bian Bingbing Xu Guo Li Feng Shi Jianhua Huang Haihuai He Yongfeng Jin A systematic CRISPR screen reveals redundant and specific roles for Dscam1 isoform diversity in neuronal wiring. PLoS Biology |
| title | A systematic CRISPR screen reveals redundant and specific roles for Dscam1 isoform diversity in neuronal wiring. |
| title_full | A systematic CRISPR screen reveals redundant and specific roles for Dscam1 isoform diversity in neuronal wiring. |
| title_fullStr | A systematic CRISPR screen reveals redundant and specific roles for Dscam1 isoform diversity in neuronal wiring. |
| title_full_unstemmed | A systematic CRISPR screen reveals redundant and specific roles for Dscam1 isoform diversity in neuronal wiring. |
| title_short | A systematic CRISPR screen reveals redundant and specific roles for Dscam1 isoform diversity in neuronal wiring. |
| title_sort | systematic crispr screen reveals redundant and specific roles for dscam1 isoform diversity in neuronal wiring |
| url | https://doi.org/10.1371/journal.pbio.3002197 |
| work_keys_str_mv | AT haiyangdong asystematiccrisprscreenrevealsredundantandspecificrolesfordscam1isoformdiversityinneuronalwiring AT xiyang asystematiccrisprscreenrevealsredundantandspecificrolesfordscam1isoformdiversityinneuronalwiring AT liliwu asystematiccrisprscreenrevealsredundantandspecificrolesfordscam1isoformdiversityinneuronalwiring AT shixinzhang asystematiccrisprscreenrevealsredundantandspecificrolesfordscam1isoformdiversityinneuronalwiring AT jianzhang asystematiccrisprscreenrevealsredundantandspecificrolesfordscam1isoformdiversityinneuronalwiring AT pengjuanguo asystematiccrisprscreenrevealsredundantandspecificrolesfordscam1isoformdiversityinneuronalwiring AT yiwendu asystematiccrisprscreenrevealsredundantandspecificrolesfordscam1isoformdiversityinneuronalwiring AT changkunpan asystematiccrisprscreenrevealsredundantandspecificrolesfordscam1isoformdiversityinneuronalwiring AT yingfu asystematiccrisprscreenrevealsredundantandspecificrolesfordscam1isoformdiversityinneuronalwiring AT leili asystematiccrisprscreenrevealsredundantandspecificrolesfordscam1isoformdiversityinneuronalwiring AT jilongshi asystematiccrisprscreenrevealsredundantandspecificrolesfordscam1isoformdiversityinneuronalwiring AT yandazhu asystematiccrisprscreenrevealsredundantandspecificrolesfordscam1isoformdiversityinneuronalwiring AT hongruma asystematiccrisprscreenrevealsredundantandspecificrolesfordscam1isoformdiversityinneuronalwiring AT linabian asystematiccrisprscreenrevealsredundantandspecificrolesfordscam1isoformdiversityinneuronalwiring AT bingbingxu asystematiccrisprscreenrevealsredundantandspecificrolesfordscam1isoformdiversityinneuronalwiring AT guoli asystematiccrisprscreenrevealsredundantandspecificrolesfordscam1isoformdiversityinneuronalwiring AT fengshi asystematiccrisprscreenrevealsredundantandspecificrolesfordscam1isoformdiversityinneuronalwiring AT jianhuahuang asystematiccrisprscreenrevealsredundantandspecificrolesfordscam1isoformdiversityinneuronalwiring AT haihuaihe asystematiccrisprscreenrevealsredundantandspecificrolesfordscam1isoformdiversityinneuronalwiring AT yongfengjin asystematiccrisprscreenrevealsredundantandspecificrolesfordscam1isoformdiversityinneuronalwiring AT haiyangdong systematiccrisprscreenrevealsredundantandspecificrolesfordscam1isoformdiversityinneuronalwiring AT xiyang systematiccrisprscreenrevealsredundantandspecificrolesfordscam1isoformdiversityinneuronalwiring AT liliwu systematiccrisprscreenrevealsredundantandspecificrolesfordscam1isoformdiversityinneuronalwiring AT shixinzhang systematiccrisprscreenrevealsredundantandspecificrolesfordscam1isoformdiversityinneuronalwiring AT jianzhang systematiccrisprscreenrevealsredundantandspecificrolesfordscam1isoformdiversityinneuronalwiring AT pengjuanguo systematiccrisprscreenrevealsredundantandspecificrolesfordscam1isoformdiversityinneuronalwiring AT yiwendu systematiccrisprscreenrevealsredundantandspecificrolesfordscam1isoformdiversityinneuronalwiring AT changkunpan systematiccrisprscreenrevealsredundantandspecificrolesfordscam1isoformdiversityinneuronalwiring AT yingfu systematiccrisprscreenrevealsredundantandspecificrolesfordscam1isoformdiversityinneuronalwiring AT leili systematiccrisprscreenrevealsredundantandspecificrolesfordscam1isoformdiversityinneuronalwiring AT jilongshi systematiccrisprscreenrevealsredundantandspecificrolesfordscam1isoformdiversityinneuronalwiring AT yandazhu systematiccrisprscreenrevealsredundantandspecificrolesfordscam1isoformdiversityinneuronalwiring AT hongruma systematiccrisprscreenrevealsredundantandspecificrolesfordscam1isoformdiversityinneuronalwiring AT linabian systematiccrisprscreenrevealsredundantandspecificrolesfordscam1isoformdiversityinneuronalwiring AT bingbingxu systematiccrisprscreenrevealsredundantandspecificrolesfordscam1isoformdiversityinneuronalwiring AT guoli systematiccrisprscreenrevealsredundantandspecificrolesfordscam1isoformdiversityinneuronalwiring AT fengshi systematiccrisprscreenrevealsredundantandspecificrolesfordscam1isoformdiversityinneuronalwiring AT jianhuahuang systematiccrisprscreenrevealsredundantandspecificrolesfordscam1isoformdiversityinneuronalwiring AT haihuaihe systematiccrisprscreenrevealsredundantandspecificrolesfordscam1isoformdiversityinneuronalwiring AT yongfengjin systematiccrisprscreenrevealsredundantandspecificrolesfordscam1isoformdiversityinneuronalwiring |