Multifold increase in spinal inhibitory cell types with emergence of limb movement Vijatovic, David Toma, Florina Alexandra Ignatyev, Y Harrington, Zoe P ; https://orcid.org/0009-0008-0158-4032 Sommer, Christoph M ; https://orcid.org/0000-0003-1216-9105 Hauschild, Robert ; https://orcid.org/0000-0001-9843-3522 Smits, Matthijs Geert Dalla Vecchia, Marco Trevisan, Alexandra J. Chapman, Phillip Julseth, Mara Brenner-Morton, Susan Gabitto, Mariano I. Dasen, Jeremy S. Bikoff, Jay B. Sweeney, Lora Beatrice Jaeger ; https://orcid.org/0000-0001-9242-5601 ddc:570 As vertebrates transitioned from water to land, locomotion shifted from undulatory swimming to limb-based movement. How spinal circuits and their cell types evolved to support this transition remains unclear. We leverage frog metamorphosis, which recapitulates this transition within a single organism, to define how spinal circuits generate aquatic versus terrestrial motor patterns. At swim stages, spinal architecture is uniform, with a transcriptionally and anatomically homogeneous motor and interneurons. As limbs develop and their movement complexifies, spinal circuits expand in neuron number and subtype diversity. This expansion is most pronounced for V1 inhibitory neurons, which increase ∼70-fold and diversify into transcriptionally distinct subtypes. Disrupting transcription factors defining emerging motor and V1 populations reveals molecular segregation between swim and limb circuits, highlighting the role of subtype diversity in motor coordination. A multifold increase in inhibitory neuron diversity thus underlies the tail-to-limb locomotor transition, providing a framework for spinal circuit adaptation during vertebrate evolution. Elsevier 2026 info:eu-repo/semantics/article doc-type:article text http://purl.org/coar/resource_type/c_2df8fbb1 https://research-explorer.ista.ac.at/record/21746 https://research-explorer.ista.ac.at/download/21746/21795 Vijatovic D, Toma FA, Ignatyev Y, et al. Multifold increase in spinal inhibitory cell types with emergence of limb movement. <i>Cell Reports</i>. 2026;45(4). doi:<a href="https://doi.org/10.1016/j.celrep.2026.117227">10.1016/j.celrep.2026.117227</a> eng info:eu-repo/semantics/altIdentifier/doi/10.1016/j.celrep.2026.117227 info:eu-repo/semantics/altIdentifier/issn/2639-1856 info:eu-repo/semantics/altIdentifier/e-issn/2211-1247 info:eu-repo/semantics/altIdentifier/pmid/41964955 info:eu-repo/semantics/openAccess