Differential adhesion regulates neurite placement via a retrograde zippering mechanism
- Yale University School of Medicine, United States
- National Institutes of Health, United States
- Sloan-Kettering Institute, United States
- Weill Cornell Medicine, United States
- University of Connecticut Health Center, United States
Abstract
During development, neurites and synapses segregate into specific neighborhoods or layers within nerve bundles. The developmental programs guiding placement of neurites in specific layers, and hence their incorporation into specific circuits, are not well understood. We implement novel imaging methods and quantitative models to document the embryonic development of the C. elegans brain neuropil, and discover that differential adhesion mechanisms control precise placement of single neurites onto specific layers. Differential adhesion is orchestrated via developmentally-regulated expression of the IgCAM SYG-1, and its partner ligand SYG-2. Changes in SYG-1 expression across neuropil layers result in changes in adhesive forces, which sort SYG-2-expressing neurons. Sorting to layers occurs, not via outgrowth from the neurite tip, but via an alternate mechanism of retrograde zippering, involving interactions between neurite shafts. Our study indicates that biophysical principles from differential adhesion govern neurite placement and synaptic specificity in vivo in developing neuropil bundles.
Data availability
All data generated or analysed during this study are included in the manuscript and supporting files. Source data files have been provided for all plots in which individual data points are not represented - Figure 4N, Figure 6K, Figure 1-figure supplement 2I, Figure 1-figure supplement 2J, Figure 5-figure supplement 4N, Figure 6-figure supplement 1C, Figure 7-figure supplement 3N
Article and author information
Author details
Daniel A Colón-Ramos
Funding
National Institutes of Health (R24-OD01647)
- Zhirong Bao
- William Mohler
- Daniel A Colón-Ramos
National Institutes of Health (NIBIB Intramural Research Program)
- Hari Shroff
National Institutes of Health (P30CA008748)
- Zhirong Bao
National Institutes of Health (R01NS076558)
- Daniel A Colón-Ramos
National Institutes of Health (DP1NS111778)
- Daniel A Colón-Ramos
Howard Hughes Medical Institute (Faculty Scholar Award)
- Daniel A Colón-Ramos
Marine Biological Laboratory (Whitman and Fellows program)
- Hari Shroff
- Daniel A Colón-Ramos
Gordon and Betty Moore Foundation (Moore Grant)
- Hari Shroff
- Daniel A Colón-Ramos
Gruber Foundation (Gruber Science Fellowship)
- Titas Sengupta
National Institutes of Health (Predoctoral Training Program in Genetics NIH 2020 T32 GM.)
- Noelle L Koonce
National Institutes of Health (F32-NS098616)
- Mark W Moyle
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Reviewing Editor
- Oliver Hobert, Howard Hughes Medical Institute, Columbia University, United States
Version history
- Received: June 11, 2021
- Accepted: November 15, 2021
- Accepted Manuscript published: November 16, 2021 (version 1)
- Version of Record published: February 10, 2022 (version 2)
Copyright
This is an open-access article, free of all copyright, and may be freely reproduced, distributed, transmitted, modified, built upon, or otherwise used by anyone for any lawful purpose. The work is made available under the Creative Commons CC0 public domain dedication.
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Differential adhesion regulates neurite placement via a retrograde zippering mechanism
eLife 10:e71171.
https://doi.org/10.7554/eLife.71171
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