Rejection of inappropriate synaptic partners in mouse retina mediated by transcellular FLRT2-UNC5 signaling.
dendrite
latrophilin
retina
retinal ganglion cell
starburst amacrine cell
synaptogenesis
Journal
Developmental cell
ISSN: 1878-1551
Titre abrégé: Dev Cell
Pays: United States
ID NLM: 101120028
Informations de publication
Date de publication:
23 10 2023
23 10 2023
Historique:
received:
06
09
2022
revised:
26
05
2023
accepted:
18
07
2023
pmc-release:
23
10
2024
medline:
27
10
2023
pubmed:
10
8
2023
entrez:
9
8
2023
Statut:
ppublish
Résumé
During nervous system development, neurons choose synaptic partners with remarkable specificity; however, the cell-cell recognition mechanisms governing rejection of inappropriate partners remain enigmatic. Here, we show that mouse retinal neurons avoid inappropriate partners by using the FLRT2-uncoordinated-5 (UNC5) receptor-ligand system. Within the inner plexiform layer (IPL), FLRT2 is expressed by direction-selective (DS) circuit neurons, whereas UNC5C/D are expressed by non-DS neurons projecting to adjacent IPL sublayers. In vivo gain- and loss-of-function experiments demonstrate that FLRT2-UNC5 binding eliminates growing DS dendrites that have strayed from the DS circuit IPL sublayers. Abrogation of FLRT2-UNC5 binding allows mistargeted arbors to persist, elaborate, and acquire synapses from inappropriate partners. Conversely, UNC5C misexpression within DS circuit sublayers inhibits dendrite growth and drives arbors into adjacent sublayers. Mechanistically, UNC5s promote dendrite elimination by interfering with FLRT2-mediated adhesion. Based on their broad expression, FLRT-UNC5 recognition is poised to exert widespread effects upon synaptic partner choices across the nervous system.
Identifiants
pubmed: 37557174
pii: S1534-5807(23)00359-3
doi: 10.1016/j.devcel.2023.07.011
pmc: PMC10615732
mid: NIHMS1920846
pii:
doi:
Substances chimiques
FLRT2 protein, mouse
0
Membrane Glycoproteins
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Research Support, N.I.H., Extramural
Langues
eng
Sous-ensembles de citation
IM
Pagination
2080-2096.e7Subventions
Organisme : NEI NIH HHS
ID : R01 EY031445
Pays : United States
Informations de copyright
Copyright © 2023 Elsevier Inc. All rights reserved.
Déclaration de conflit d'intérêts
Declaration of interests The authors declare no competing interests.
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