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    Differential adhesion regulates neurite placement via a retrograde zippering mechanism

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    漏 The Author(s), 2021. This article is distributed under the terms of the Creative Commons Attribution License. The definitive version was published in Sengupta, T., Koonce, N. L., Vazquez-Martinez, N., Moyle, M. W., Duncan, L. H., Emerson, S. E., Han, X., Shao, L., Wu, Y., Santella, A., Fan, L., Bao, Z., Mohler, W. A., Shroff, H., & Colon-Ramos, D. A. Differential adhesion regulates neurite placement via a retrograde zippering mechanism. Elife, 10, (2021): e71171, https://doi.org/10.7554/eLife.71171.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.National Institutes of Health (R24-OD01647) Zhirong Bao William Mohler Daniel A Col贸n-Ramos National Institutes of Health (R01NS076558) Daniel A Col贸n-Ramos National Institutes of Health (DP1NS111778) Daniel A Col贸n-Ramos Howard Hughes Medical Institute (Faculty Scholar Award) Daniel A Col贸n-Ramos Marine Biological Laboratory (Whitman and Fellows program) Hari Shroff Daniel A Col贸n-Ramos Gordon and Betty Moore Foundation (Moore Grant) Hari Shroff Daniel A Col贸n-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 National Institutes of Health (NIBIB Intramural Research Program) Hari Shroff National Institutes of Health (P30CA008748) Zhirong Ba
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