In:
PLOS Biology, Public Library of Science (PLoS), Vol. 21, No. 7 ( 2023-7-6), p. e3002197-
Abstract:
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.
Type of Medium:
Online Resource
ISSN:
1545-7885
DOI:
10.1371/journal.pbio.3002197
DOI:
10.1371/journal.pbio.3002197.g001
DOI:
10.1371/journal.pbio.3002197.g002
DOI:
10.1371/journal.pbio.3002197.g003
DOI:
10.1371/journal.pbio.3002197.g004
DOI:
10.1371/journal.pbio.3002197.g005
DOI:
10.1371/journal.pbio.3002197.g006
DOI:
10.1371/journal.pbio.3002197.g007
DOI:
10.1371/journal.pbio.3002197.s001
DOI:
10.1371/journal.pbio.3002197.s002
DOI:
10.1371/journal.pbio.3002197.s003
DOI:
10.1371/journal.pbio.3002197.s004
DOI:
10.1371/journal.pbio.3002197.s005
DOI:
10.1371/journal.pbio.3002197.s006
DOI:
10.1371/journal.pbio.3002197.s007
DOI:
10.1371/journal.pbio.3002197.s008
DOI:
10.1371/journal.pbio.3002197.s009
DOI:
10.1371/journal.pbio.3002197.s010
DOI:
10.1371/journal.pbio.3002197.s011
DOI:
10.1371/journal.pbio.3002197.s012
DOI:
10.1371/journal.pbio.3002197.s013
DOI:
10.1371/journal.pbio.3002197.s014
DOI:
10.1371/journal.pbio.3002197.s015
DOI:
10.1371/journal.pbio.3002197.s016
Language:
English
Publisher:
Public Library of Science (PLoS)
Publication Date:
2023
detail.hit.zdb_id:
2126773-X
Permalink