Ploidy and neuron size impact nervous system development and function in Xenopus

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 the effects of neuron size on the vertebrate nervous system, we characterized triploid Xenopus tadpoles, which possess a 1.5-fold increase in genome size compared with diploids. Triploid neurons displayed a scaling increase in total volume and a superscaling increase in membrane surface area. Imaging, flow cytometry, and RNA sequencing 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.