The absence of BBSome function decreases synaptogenesis and causes ectopic synapse formation in the retina

Ying Hsu; Janelle E Garrison; Seongjin Seo; Val C Sheffield

doi:10.1038/s41598-020-65233-4

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The absence of BBSome function decreases synaptogenesis and causes ectopic synapse formation in the retina

Journal article

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The absence of BBSome function decreases synaptogenesis and causes ectopic synapse formation in the retina

Ying Hsu, Janelle E Garrison, Seongjin Seo and Val C Sheffield

Scientific reports, Vol.10(1), pp.8321-8321

05/20/2020

DOI: 10.1038/s41598-020-65233-4

PMCID: PMC7239920

PMID: 32433491

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https://doi.org/10.1038/s41598-020-65233-4View

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Abstract

Photoreceptors possess ribbon synapses distinct from the conventional synapses in the brain. Little is known about the function of the BBSome, a complex integral in ciliary and intracellular trafficking, in ribbon synaptic formation. We performed immunohistochemistry using retinas from Bardet-Biedl Syndrome (BBS) mouse models and found that BBS mutant animals have significantly fewer ribbon synapses in the outer plexiform layer and increased ectopic synapses in the outer nuclear layer compared to controls. Many ectopic synapses in BBS mutant retinas are associated with horizontal cell axonal processes that aberrantly intrude into the outer nuclear layer. To determine whether this horizontal cell phenotype is a consequence of retinal degeneration, we examined this phenotype in mice with photoreceptor-specific inactivation of the BBSome induced by Cre recombinase driven by the rhodopsin promoter. At three months of age, despite retinal degeneration, Bbs8 ; Rho-Cre mice lack the aberrant intrusion of horizontal cell processes. At 6 months, some horizontal cell processes intrude into the outer nuclear layer in Bbs8 ; Rho-Cre mice, but the phenotype does not recapitulate the phenotypic severity observed in young congenital BBS mutant mice. Therefore, the lack of BBSome function negatively impacts retinal synaptogenesis, and causes horizontal cell defects in a potentially cell-autonomous fashion.

Cilia - physiology

Proteins - physiology

Cytoskeletal Proteins - genetics

Male

Multiprotein Complexes - genetics

Synapses - pathology

Neurogenesis

Mice, Knockout

Multiprotein Complexes - physiology

Proteins - genetics

Animals

Bardet-Biedl Syndrome

Female

Mice

Photoreceptor Cells - pathology

Cytoskeletal Proteins - physiology

Retinal Degeneration - pathology

Photoreceptor Cells - physiology

Retina - pathology

Details

Title: Subtitle: The absence of BBSome function decreases synaptogenesis and causes ectopic synapse formation in the retina
Creators: Ying Hsu - Molecular Medicine Graduate Program, University of Iowa, Iowa City, United States
Janelle E Garrison - Department of Pediatrics, Division of Medical Genetics and Genomics, University of Iowa Carver College of Medicine, 4181 MERF, 375 Newton Road, 52242, Iowa City, Iowa, United States
Seongjin Seo - Department of Ophthalmology and Visual Sciences, University of Iowa, Iowa City, Iowa, 52242, United States
Val C Sheffield - Department of Ophthalmology and Visual Sciences, University of Iowa, Iowa City, Iowa, 52242, United States. val-sheffield@uiowa.edu
Resource Type: Journal article
Publication Details: Scientific reports, Vol.10(1), pp.8321-8321
DOI: 10.1038/s41598-020-65233-4
PMID: 32433491
PMCID: PMC7239920
NLM abbreviation: Sci Rep
ISSN: 2045-2322
eISSN: 2045-2322
Publisher: England
Grant note: R01 EY011298 / NEI NIH HHS P30 EY025580 / NEI NIH HHS R01 EY022616 / NEI NIH HHS R21 EY027431 / NEI NIH HHS R01 EY030366 / NEI NIH HHS R01 EY017168 / NEI NIH HHS
Language: English
Date published: 05/20/2020
Academic Unit: Stead Family Department of Pediatrics; Iowa Neuroscience Institute; Medical Genetics and Genomics; Ophthalmology and Visual Sciences
Record Identifier: 9984070595502771

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