Differential adhesion regulates neurite placement via a retrograde zippering mechanism

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.

Automated summary

In the development of C. elegans brain neuropil, differential adhesion mechanisms controlled by IgCAM SYG-1 and SYG-2 play a crucial role in precise placement of single neurites onto specific layers. Neuronal sorting to layers occurs through retrograde zippering between neurite shafts, rather than outgrowth from the neurite tip. This study suggests that differential adhesion governs neurite placement and synaptic specificity in developing neuropil bundles.