Spinal neuron diversity scales exponentially with swim-to-limb transformation during frog metamorphosis

preprint Spinal neuron diversity scales exponentially with swim-to-limb transformation during frog metamorphosis submitted David Vijatovic author cf391e77-ec3c-11ea-a124-d69323410b58 Florina Alexandra Toma author 2f73f876-f128-11eb-9611-b96b5a30cb0e Zoe P Harrington author a8144562-32c9-11ee-b5ce-d9800628bda20009-0008-0158-4032 Christoph M Sommer author 4DF26D8C-F248-11E8-B48F-1D18A9856A870000-0003-1216-9105 Robert Hauschild author 4E01D6B4-F248-11E8-B48F-1D18A9856A870000-0001-9843-3522 Alexandra J. Trevisan author Phillip Chapman author Mara Julseth author 1cf464b2-dc7d-11ea-9b2f-f9b1aa9417d1 Susan Brenner-Morton author Mariano I. Gabitto author Jeremy S. Dasen author Jay B. Bikoff author Lora Beatrice Jaeger Sweeney author 56BE8254-C4F0-11E9-8E45-0B23E66974250000-0001-9242-5601 LoSw department TiVo department Bio department NiBa department Development of V1 interneuron diversity during swim-to-walk transition of Xenopus metamorphosis project Development and Evolution of Tetrapod Motor Circuits project Tools for automation and feedback microscopy project Vertebrates exhibit a wide range of motor behaviors, ranging from swimming to complex limb-based movements. Here we take advantage of frog metamorphosis, which captures a swim-to-limb-based movement transformation during the development of a single organism, to explore changes in the underlying spinal circuits. We find that the tadpole spinal cord contains small and largely homogeneous populations of motor neurons (MNs) and V1 interneurons (V1s) at early escape swimming stages. These neuronal populations only modestly increase in number and subtype heterogeneity with the emergence of free swimming. In contrast, during frog metamorphosis and the emergence of limb movement, there is a dramatic expansion of MN and V1 interneuron number and transcriptional heterogeneity, culminating in cohorts of neurons that exhibit striking molecular similarity to mammalian motor circuits. CRISPR/Cas9-mediated gene disruption of the limb MN and V1 determinants FoxP1 and Engrailed-1, respectively, results in severe but selective deficits in tail and limb function. Our work thus demonstrates that neural diversity scales exponentially with increasing behavioral complexity and illustrates striking evolutionary conservation in the molecular organization and function of motor circuits across species. 2024 eng bioRxiv10.1101/2024.09.20.614050 Vijatovic D, Toma FA, Harrington ZP, Sommer CM, Hauschild R, Trevisan AJ, Chapman P, Julseth M, Brenner-Morton S, Gabitto MI, Dasen JS, Bikoff JB, Sweeney LB. Spinal neuron diversity scales exponentially with swim-to-limb transformation during frog metamorphosis. bioRxiv, <a href="https://doi.org/10.1101/2024.09.20.614050">10.1101/2024.09.20.614050</a>. D. Vijatovic, F.A. Toma, Z.P. Harrington, C.M. Sommer, R. Hauschild, A.J. Trevisan, P. Chapman, M. Julseth, S. Brenner-Morton, M.I. Gabitto, J.S. Dasen, J.B. Bikoff, L.B. Sweeney, BioRxiv (n.d.). D. Vijatovic et al., “Spinal neuron diversity scales exponentially with swim-to-limb transformation during frog metamorphosis,” bioRxiv. . Vijatovic, David, Florina Alexandra Toma, Zoe P Harrington, Christoph M Sommer, Robert Hauschild, Alexandra J. Trevisan, Phillip Chapman, et al. “Spinal Neuron Diversity Scales Exponentially with Swim-to-Limb Transformation during Frog Metamorphosis.” BioRxiv, n.d. <a href="https://doi.org/10.1101/2024.09.20.614050">https://doi.org/10.1101/2024.09.20.614050</a>. Vijatovic, D., Toma, F. A., Harrington, Z. P., Sommer, C. M., Hauschild, R., Trevisan, A. J., … Sweeney, L. B. (n.d.). Spinal neuron diversity scales exponentially with swim-to-limb transformation during frog metamorphosis. bioRxiv. <a href="https://doi.org/10.1101/2024.09.20.614050">https://doi.org/10.1101/2024.09.20.614050</a> Vijatovic, David, et al. “Spinal Neuron Diversity Scales Exponentially with Swim-to-Limb Transformation during Frog Metamorphosis.” BioRxiv, doi:<a href="https://doi.org/10.1101/2024.09.20.614050">10.1101/2024.09.20.614050</a>. Vijatovic D, Toma FA, Harrington ZP, et al. Spinal neuron diversity scales exponentially with swim-to-limb transformation during frog metamorphosis. bioRxiv. doi:<a href="https://doi.org/10.1101/2024.09.20.614050">10.1101/2024.09.20.614050</a> 195202025-04-07T08:48:28Z2025-05-14T11:40:13Z