Semaphorin 3f and post-embryonic regulation of retinal progenitors.

Neural progenitors produce specific cell types that form the circuits of the nervous system. Extrinsic signals regulate both progenitor proliferation and the production of specific neuron types. Where progenitors reside within a progenitor niche determines to which of these signals they are exposed,...

Full description

Saved in:
Bibliographic Details
Main Authors: Amira Kalifa, Carrie L Hehr, Katelyn L Shewchuk, Risa Mori-Kreiner, Shaelene Standing, Rami Halabi, Sarah McFarlane
Format: Article
Language:English
Published: Public Library of Science (PLoS) 2025-07-01
Series:PLoS Genetics
Online Access:https://doi.org/10.1371/journal.pgen.1011748
Tags: Add Tag
No Tags, Be the first to tag this record!
_version_ 1850095735093067776
author Amira Kalifa
Carrie L Hehr
Katelyn L Shewchuk
Risa Mori-Kreiner
Shaelene Standing
Rami Halabi
Sarah McFarlane
author_facet Amira Kalifa
Carrie L Hehr
Katelyn L Shewchuk
Risa Mori-Kreiner
Shaelene Standing
Rami Halabi
Sarah McFarlane
author_sort Amira Kalifa
collection DOAJ
description Neural progenitors produce specific cell types that form the circuits of the nervous system. Extrinsic signals regulate both progenitor proliferation and the production of specific neuron types. Where progenitors reside within a progenitor niche determines to which of these signals they are exposed, and thus likely has important consequences on the progeny they produce. Little is known, however, of the signals that govern progenitor location within the niche. Here we show that a member of the Class III family of secreted Semaphorins, Semaphorin3fa (Sema3fa), is required for the orderly arrangement of progenitors with a niche present in the periphery of the larval and adult retina of zebrafish, the ciliary marginal zone (CMZ). CMZ progenitors express mRNAs for various Sema3 receptors, including for nrp2a, nrp2b and plxna1. Loss of Sema3fa in a previously characterized CRISPR/Cas9-generated sema3fa mutant allele (sema3faca304) results in a reduced eye size in juvenile fish, implicating Sema3fa in the ongoing production of retinal cells by the CMZ. Larval progenitors show altered cell cycle parameters, and the spatial organization of functionally distinct progenitors is disrupted, as is the generation of retinal cell types in the appropriate proportions and numbers. Our data support a model whereby Sema3fa secreted by CMZ progenitors reduces adhesive interactions to allow for smooth progression of progenitors through the niche, ensuring progenitors receive the correct recipe of extrinsic signals to secure the proper generation of new retinal circuits.
format Article
id doaj-art-528ab4ab96eb47edac72e3885aef67e1
institution DOAJ
issn 1553-7390
1553-7404
language English
publishDate 2025-07-01
publisher Public Library of Science (PLoS)
record_format Article
series PLoS Genetics
spelling doaj-art-528ab4ab96eb47edac72e3885aef67e12025-08-20T02:41:23ZengPublic Library of Science (PLoS)PLoS Genetics1553-73901553-74042025-07-01217e101174810.1371/journal.pgen.1011748Semaphorin 3f and post-embryonic regulation of retinal progenitors.Amira KalifaCarrie L HehrKatelyn L ShewchukRisa Mori-KreinerShaelene StandingRami HalabiSarah McFarlaneNeural progenitors produce specific cell types that form the circuits of the nervous system. Extrinsic signals regulate both progenitor proliferation and the production of specific neuron types. Where progenitors reside within a progenitor niche determines to which of these signals they are exposed, and thus likely has important consequences on the progeny they produce. Little is known, however, of the signals that govern progenitor location within the niche. Here we show that a member of the Class III family of secreted Semaphorins, Semaphorin3fa (Sema3fa), is required for the orderly arrangement of progenitors with a niche present in the periphery of the larval and adult retina of zebrafish, the ciliary marginal zone (CMZ). CMZ progenitors express mRNAs for various Sema3 receptors, including for nrp2a, nrp2b and plxna1. Loss of Sema3fa in a previously characterized CRISPR/Cas9-generated sema3fa mutant allele (sema3faca304) results in a reduced eye size in juvenile fish, implicating Sema3fa in the ongoing production of retinal cells by the CMZ. Larval progenitors show altered cell cycle parameters, and the spatial organization of functionally distinct progenitors is disrupted, as is the generation of retinal cell types in the appropriate proportions and numbers. Our data support a model whereby Sema3fa secreted by CMZ progenitors reduces adhesive interactions to allow for smooth progression of progenitors through the niche, ensuring progenitors receive the correct recipe of extrinsic signals to secure the proper generation of new retinal circuits.https://doi.org/10.1371/journal.pgen.1011748
spellingShingle Amira Kalifa
Carrie L Hehr
Katelyn L Shewchuk
Risa Mori-Kreiner
Shaelene Standing
Rami Halabi
Sarah McFarlane
Semaphorin 3f and post-embryonic regulation of retinal progenitors.
PLoS Genetics
title Semaphorin 3f and post-embryonic regulation of retinal progenitors.
title_full Semaphorin 3f and post-embryonic regulation of retinal progenitors.
title_fullStr Semaphorin 3f and post-embryonic regulation of retinal progenitors.
title_full_unstemmed Semaphorin 3f and post-embryonic regulation of retinal progenitors.
title_short Semaphorin 3f and post-embryonic regulation of retinal progenitors.
title_sort semaphorin 3f and post embryonic regulation of retinal progenitors
url https://doi.org/10.1371/journal.pgen.1011748
work_keys_str_mv AT amirakalifa semaphorin3fandpostembryonicregulationofretinalprogenitors
AT carrielhehr semaphorin3fandpostembryonicregulationofretinalprogenitors
AT katelynlshewchuk semaphorin3fandpostembryonicregulationofretinalprogenitors
AT risamorikreiner semaphorin3fandpostembryonicregulationofretinalprogenitors
AT shaelenestanding semaphorin3fandpostembryonicregulationofretinalprogenitors
AT ramihalabi semaphorin3fandpostembryonicregulationofretinalprogenitors
AT sarahmcfarlane semaphorin3fandpostembryonicregulationofretinalprogenitors