TY - JOUR
T1 - Synapse maintenance and restoration in the retina by NGL2
AU - Soto, Florentina
AU - Zhao, Lei
AU - Kerschensteiner, Daniel
N1 - Funding Information:
We thank members of the Kerschensteiner lab for helpful comments and suggestions throughout this study. We thank Michael Casey of the Vision Core at Washington University School of Medicine for help with the design of sgRNAs and the construction of plasmids. We acknowledge the Genome Engineering and iPSC Center (GEiC) at Washington University School of Medicine for validating sgRNAs in vitro. We are grateful to Drs. A Ghosh and L DeNardo for providing us with the mouse Ngl2 cDNA. This work was supported by the National Institutes of Health (EY027411 to FS and DK, EY026978 and EY023341 to DK, and the Vision Core Grant EY0268), and by the Research to Prevent Blindness Foundation via an unrestricted grant to the Department of Ophthalmology and Visual Sciences at Washington University School of Medicine.
Publisher Copyright:
© Soto et al.
PY - 2018/3/19
Y1 - 2018/3/19
N2 - Synaptic cell adhesion molecules (CAMs) promote synapse formation in the developing nervous system. To what extent they maintain and can restore connections in the mature nervous system is unknown. Furthermore, how synaptic CAMs affect the growth of synapse-bearing neurites is unclear. Here, we use adeno-associated viruses (AAVs) to delete, re-, and overexpress the synaptic CAM NGL2 in individual retinal horizontal cells. When we removed NGL2 from horizontal cells, their axons overgrew and formed fewer synapses, irrespective of whether Ngl2 was deleted during development or in mature circuits. When we re-expressed NGL2 in knockout mice, horizontal cell axon territories and synapse numbers were restored, even if AAVs were injected after phenotypes had developed. Finally, overexpression of NGL2 in wild-type horizontal cells elevated synapse numbers above normal levels. Thus, NGL2 promotes the formation, maintenance, and restoration of synapses in the developing and mature retina, and restricts axon growth throughout life.
AB - Synaptic cell adhesion molecules (CAMs) promote synapse formation in the developing nervous system. To what extent they maintain and can restore connections in the mature nervous system is unknown. Furthermore, how synaptic CAMs affect the growth of synapse-bearing neurites is unclear. Here, we use adeno-associated viruses (AAVs) to delete, re-, and overexpress the synaptic CAM NGL2 in individual retinal horizontal cells. When we removed NGL2 from horizontal cells, their axons overgrew and formed fewer synapses, irrespective of whether Ngl2 was deleted during development or in mature circuits. When we re-expressed NGL2 in knockout mice, horizontal cell axon territories and synapse numbers were restored, even if AAVs were injected after phenotypes had developed. Finally, overexpression of NGL2 in wild-type horizontal cells elevated synapse numbers above normal levels. Thus, NGL2 promotes the formation, maintenance, and restoration of synapses in the developing and mature retina, and restricts axon growth throughout life.
UR - http://www.scopus.com/inward/record.url?scp=85045640531&partnerID=8YFLogxK
U2 - 10.7554/eLife.30388
DO - 10.7554/eLife.30388
M3 - Article
C2 - 29553369
AN - SCOPUS:85045640531
SN - 2050-084X
VL - 7
JO - eLife
JF - eLife
M1 - e30388
ER -