LKB1 coordinates neurite remodeling to drive synapse layer emergence in the outer retina
- Baylor College of Medicine, United States
- David Geffen School of Medicine, University of California, Los Angeles, United States
Abstract
Structural changes in pre and postsynaptic neurons that accompany synapse formation often temporally and spatially overlap. Thus, it has been difficult to resolve which processes drive patterned connectivity. To overcome this, we use the laminated outer murine retina. We identify the serine/threonine kinase LKB1 as a key driver of synapse layer emergence. The absence of LKB1 in the retina caused a marked mislocalization and delay in synapse layer formation. In parallel, LKB1 modulated postsynaptic horizontal cell refinement and presynaptic photoreceptor axon growth. Mislocalized horizontal cell processes contacted aberrant cone axons in LKB1 mutants. These defects coincided with altered synapse protein organization, and horizontal cell neurites were misdirected to ectopic synapse protein regions. Together, these data suggest that LKB1 instructs the timing and location of connectivity in the outer retina via coordinate regulation of pre and postsynaptic neuron structure and the localization of synapse-associated proteins.
Data availability
Source data analysis code have been provided from Figures 1-4.
Article and author information
Author details
Funding
National Institute on Aging (1R56AG061808-01)
- Melanie A Samuel
National Eye Institute (R01 EY030458-01)
- Melanie A Samuel
Ted Nash Foundation
- Melanie A Samuel
Brain Reserach Foundation
- Melanie A Samuel
National Eye Institute (DP2EY027984-02)
- Melanie A Samuel
National Eye Institute (T32EY007001)
- Courtney A Burger
National Institute of General Medical Sciences (T32GM088129)
- Nicholas E Albrecht
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Ethics
Animal experimentation: Experiments were carried out in male and female mice in accordance with the recommendations in the Guide for the Care and Use of Laboratory Animals of the NIH under protocols approved by the BCM Institutional Animal Care and Use Committee (AN6785). Every effort was made to minimize animal suffering.
Reviewing Editor
- Gary L Westbrook, Oregon Health and Science University, United States
Publication history
- Received: March 25, 2020
- Accepted: April 11, 2020
- Accepted Manuscript published: May 7, 2020 (version 1)
- Version of Record published: May 19, 2020 (version 2)
Copyright
© 2020, Burger et al.
This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.
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LKB1 coordinates neurite remodeling to drive synapse layer emergence in the outer retina
eLife 9:e56931.
https://doi.org/10.7554/eLife.56931
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