Liu, X.; Wan, C.; Shah, S. A.; Heald, R.

Neuron size varies significantly over evolution, contributing to diverse nervous systems of variable complexity, while aberrant neuron size is associated with neurodevelopmental and degenerative diseases. How do neuron cell body and neurite size and organization impact nervous system development and function? To systematically study effects of neuron size on the vertebrate nervous system, we characterized triploid Xenopus tadpoles that possess a 1.5-fold increase in genome size compared to diploids. Triploids displayed a linear increase in total neuronal volume and a superlinear increase in membrane surface area. Imaging, flow cytometry, and RNA-seq analyses revealed that triploid brains were morphologically and transcriptionally similar to diploid brains, but less proliferative, containing fewer neurons and displaying increased global activity. Interestingly, physiological differences at the neuron and nervous system levels affected swimming behavior in tadpoles. Our findings thus establish a framework to link genome size, neuron size, and nervous system development and function in vertebrates.