Multifold increase in spinal inhibitory cell types with emergence of limb movement
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.
Authors
- Robert Hauschild (ORCID: https://orcid.org/0000-0001-9843-3522)
- Alexandra J. Trevisan
- Yuri Ignatyev (ORCID: https://orcid.org/0009-0009-7251-0046)
- Jay B. Bikoff
- Mariano I. Gabitto (ORCID: https://orcid.org/0000-0001-6911-344X)
- F. Toma (ORCID: https://orcid.org/0009-0005-3473-2968)
- Lora B. Sweeney (ORCID: https://orcid.org/0000-0001-9242-5601)
- Marco Dalla Vecchia
- Jeremy S. Dasen (ORCID: https://orcid.org/0000-0002-9434-874X)
- David Vijatovic (ORCID: https://orcid.org/0000-0002-5494-0941)
- Christoph Sommer (ORCID: https://orcid.org/0000-0003-1216-9105)
- Susan Brenner-Morton
- Mara J. Julseth
- Zoe P.M. Harrington
- Matthjis Smits
- Phillip Chapman
Institutions
- St. Jude Children's Research Hospital (US)
- Institute of Science and Technology Austria (AT)
- Neurosciences Institute (US)
- Allen Institute (US)
- Columbia University (US)
Publication Details
- Journal
- Cell Reports
- Published
- 2026-04-01
- DOI
- https://doi.org/10.1016/j.celrep.2026.117227
- Primary Topic
- Axon Guidance and Neuronal Signaling
- Type
- article
- Field-Weighted Citation Impact
- 0.00
Funders
- American Lebanese Syrian Associated Charities
- Institute of Science and Technology Austria
- Chan Zuckerberg Initiative
- Gesellschaft für Forschungsförderung Niederösterreich
- Deutscher Akademischer Austauschdienst
- Austrian Science Fund
- European Research Council
- National Institute of Neurological Disorders and Stroke
- HORIZON EUROPE European Research Council