Department of Neuroscience and Department of Cell Biology, Yale University School of Medicine, New Haven, United States
Noelle L Koonce
Department of Neuroscience and Department of Cell Biology, Yale University School of Medicine, New Haven, United States
Nabor Vázquez-Martínez
Department of Neuroscience and Department of Cell Biology, Yale University School of Medicine, New Haven, United States
Mark W Moyle
Department of Neuroscience and Department of Cell Biology, Yale University School of Medicine, New Haven, United States
Leighton H Duncan
Department of Neuroscience and Department of Cell Biology, Yale University School of Medicine, New Haven, United States
Sarah E Emerson
Department of Neuroscience and Department of Cell Biology, Yale University School of Medicine, New Haven, United States
Xiaofei Han
Laboratory of High Resolution Optical Imaging, National Institute of Biomedical Imaging and Bioengineering, National Institutes of Health, Bethesda, United States
Lin Shao
Department of Neuroscience and Department of Cell Biology, Yale University School of Medicine, New Haven, United States
Yicong Wu
Laboratory of High Resolution Optical Imaging, National Institute of Biomedical Imaging and Bioengineering, National Institutes of Health, Bethesda, United States
Anthony Santella
Developmental Biology Program, Sloan Kettering Institute, New Haven, United States
Li Fan
Developmental Biology Program, Sloan Kettering Institute, New Haven, United States
Developmental Biology Program, Sloan Kettering Institute, New Haven, United States
William A Mohler
Department of Genetics and Genome Sciences and Center for Cell Analysis and Modeling, University of Connecticut Health Center, Farmington, United States
Hari Shroff
Laboratory of High Resolution Optical Imaging, National Institute of Biomedical Imaging and Bioengineering, National Institutes of Health, Bethesda, United States; MBL Fellows, Marine Biological Laboratory, Woods Hole, United States
Department of Neuroscience and Department of Cell Biology, Yale University School of Medicine, New Haven, United States; MBL Fellows, Marine Biological Laboratory, Woods Hole, United States; Wu Tsai Institute, Yale University, New Haven, United States; Instituto de Neurobiología, Recinto de Ciencias Médicas, Universidad de Puerto Rico, San Juan, Puerto Rico
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.
