Howard Hughes Medical Institute and Laboratory of Sensory Neuroscience, The Rockefeller University, New York City, United States; Tri-Institutional PhD Program in Computational Biology and Medicine, New York, United States
Sang Peter Paik
Howard Hughes Medical Institute and Laboratory of Sensory Neuroscience, The Rockefeller University, New York City, United States
Lauren M Snow
Howard Hughes Medical Institute and Laboratory of Sensory Neuroscience, The Rockefeller University, New York City, United States
Adrian Jacobo
Howard Hughes Medical Institute and Laboratory of Sensory Neuroscience, The Rockefeller University, New York City, United States; Chan Zuckerberg Biohub San Francisco, San Francisco, United States
In a developing nervous system, axonal arbors often undergo complex rearrangements before neural circuits attain their final innervation topology. In the lateral line sensory system of the zebrafish, developing sensory axons reorganize their terminal arborization patterns to establish precise neural microcircuits around the mechanosensory hair cells. However, a quantitative understanding of the changes in the sensory arbor morphology and the regulators behind the microcircuit assembly remain enigmatic. Here, we report that Semaphorin7A (Sema7A) acts as an important mediator of these processes. Utilizing a semi-automated three-dimensional neurite tracing methodology and computational techniques, we have identified and quantitatively analyzed distinct topological features that shape the network in wild-type and Sema7A loss-of-function mutants. In contrast to those of wild-type animals, the sensory axons in Sema7A mutants display aberrant arborizations with disorganized network topology and diminished contacts to hair cells. Moreover, ectopic expression of a secreted form of Sema7A by non-hair cells induces chemotropic guidance of sensory axons. Our findings propose that Sema7A likely functions both as a juxtracrine and as a secreted cue to pattern neural circuitry during sensory organ development.
