---
DOAJ_listed: '1'
OA_place: publisher
OA_type: gold
PlanS_conform: '1'
_id: '21746'
abstract:
- lang: eng
text: 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.
acknowledged_ssus:
- _id: Bio
- _id: LifeSc
acknowledgement: 'We would like to thank the members of the Sweeney Lab, Mario de
Bono, Michael Forsthofer, Katharina Lust, and Meital Oren, for comments on the manuscript.
We are also grateful to Tom Jessell and Chris Kintner for their scientific insight
and mentorship during the conception of this project. It would also have not been
possible without the technical support of the Aquatics and Imaging and Optics Facility
support teams (ISTA). We thank Martin Estermann for preparing the initial draft
of the graphical abstract and Niki Barolini for the final version. In addition,
we thank our funding sources for providing the resources to do these experiments:
GFF NÖ FTI Strategy Lower Austria dissertation grant FT121-D-046 (to D.V.), Horizon
Europe ERC starting grant 101041551 (to Y.I., L.B.S., F.A.T., and D.V.), Special
Research Program (SFB) of the Austrian Science Fund (FWF) project F7814-B (to L.B.S.),
Austrian Science Fund (FWF) 10.55776/COE16 (to Y.I. and L.B.S.), NINDS 5R35NS116858
(to J.S.D.), CZI grant DAF2020-225401 (DOI) 10.37921/120055ratwvi (to R.H.), NIH
grant R01NS123116 (to J.B.B.), American Lebanese Syrian Associated Charities (ALSAC)
(to J.B.B.), German Academic Exchange Service (DAAD) IFI grant 57515251-91853472
(to Z.H.), and Project A.L.S. (to S.B.-M.).'
article_number: '117227'
article_processing_charge: Yes
article_type: original
author:
- first_name: David
full_name: Vijatovic, David
id: cf391e77-ec3c-11ea-a124-d69323410b58
last_name: Vijatovic
- first_name: 'Florina Alexandra '
full_name: 'Toma, Florina Alexandra '
id: 2f73f876-f128-11eb-9611-b96b5a30cb0e
last_name: Toma
- first_name: Y
full_name: Ignatyev, Y
last_name: Ignatyev
- first_name: Zoe P
full_name: Harrington, Zoe P
id: a8144562-32c9-11ee-b5ce-d9800628bda2
last_name: Harrington
orcid: 0009-0008-0158-4032
- first_name: Christoph M
full_name: Sommer, Christoph M
id: 4DF26D8C-F248-11E8-B48F-1D18A9856A87
last_name: Sommer
orcid: 0000-0003-1216-9105
- first_name: Robert
full_name: Hauschild, Robert
id: 4E01D6B4-F248-11E8-B48F-1D18A9856A87
last_name: Hauschild
orcid: 0000-0001-9843-3522
- first_name: Matthijs Geert
full_name: Smits, Matthijs Geert
id: 7a231d52-e216-11ee-a0bb-8acd55f8f1f0
last_name: Smits
- first_name: Marco
full_name: Dalla Vecchia, Marco
id: 02a7a869-ff06-11ed-a87f-86649d6077e5
last_name: Dalla Vecchia
- first_name: Alexandra J.
full_name: Trevisan, Alexandra J.
last_name: Trevisan
- first_name: Phillip
full_name: Chapman, Phillip
last_name: Chapman
- first_name: Mara
full_name: Julseth, Mara
id: 1cf464b2-dc7d-11ea-9b2f-f9b1aa9417d1
last_name: Julseth
- first_name: Susan
full_name: Brenner-Morton, Susan
last_name: Brenner-Morton
- first_name: Mariano I.
full_name: Gabitto, Mariano I.
last_name: Gabitto
- first_name: Jeremy S.
full_name: Dasen, Jeremy S.
last_name: Dasen
- first_name: Jay B.
full_name: Bikoff, Jay B.
last_name: Bikoff
- first_name: Lora Beatrice Jaeger
full_name: Sweeney, Lora Beatrice Jaeger
id: 56BE8254-C4F0-11E9-8E45-0B23E6697425
last_name: Sweeney
orcid: 0000-0001-9242-5601
citation:
ama: Vijatovic D, Toma FA, Ignatyev Y, et al. Multifold increase in spinal inhibitory
cell types with emergence of limb movement. Cell Reports. 2026;45(4). doi:10.1016/j.celrep.2026.117227
apa: Vijatovic, D., Toma, F. A., Ignatyev, Y., Harrington, Z. P., Sommer, C. M.,
Hauschild, R., … Sweeney, L. B. (2026). Multifold increase in spinal inhibitory
cell types with emergence of limb movement. Cell Reports. Elsevier. https://doi.org/10.1016/j.celrep.2026.117227
chicago: Vijatovic, David, Florina Alexandra Toma, Y Ignatyev, Zoe P Harrington,
Christoph M Sommer, Robert Hauschild, Matthijs Geert Smits, et al. “Multifold
Increase in Spinal Inhibitory Cell Types with Emergence of Limb Movement.” Cell
Reports. Elsevier, 2026. https://doi.org/10.1016/j.celrep.2026.117227.
ieee: D. Vijatovic et al., “Multifold increase in spinal inhibitory cell
types with emergence of limb movement,” Cell Reports, vol. 45, no. 4. Elsevier,
2026.
ista: Vijatovic D, Toma FA, Ignatyev Y, Harrington ZP, Sommer CM, Hauschild R, Smits
MG, Dalla Vecchia M, Trevisan AJ, Chapman P, Julseth M, Brenner-Morton S, Gabitto
MI, Dasen JS, Bikoff JB, Sweeney LB. 2026. Multifold increase in spinal inhibitory
cell types with emergence of limb movement. Cell Reports. 45(4), 117227.
mla: Vijatovic, David, et al. “Multifold Increase in Spinal Inhibitory Cell Types
with Emergence of Limb Movement.” Cell Reports, vol. 45, no. 4, 117227,
Elsevier, 2026, doi:10.1016/j.celrep.2026.117227.
short: D. Vijatovic, F.A. Toma, Y. Ignatyev, Z.P. Harrington, C.M. Sommer, R. Hauschild,
M.G. Smits, M. Dalla Vecchia, A.J. Trevisan, P. Chapman, M. Julseth, S. Brenner-Morton,
M.I. Gabitto, J.S. Dasen, J.B. Bikoff, L.B. Sweeney, Cell Reports 45 (2026).
corr_author: '1'
date_created: 2026-04-19T22:07:43Z
date_published: 2026-04-28T00:00:00Z
date_updated: 2026-05-04T12:27:06Z
day: '28'
ddc:
- '570'
department:
- _id: LoSw
- _id: GradSch
- _id: TiVo
- _id: Bio
- _id: NiBa
doi: 10.1016/j.celrep.2026.117227
external_id:
pmid:
- '41964955 '
file:
- access_level: open_access
checksum: 0d26cdb5b8d8dec3a911d8261a65cdef
content_type: application/pdf
creator: dernst
date_created: 2026-05-04T12:20:10Z
date_updated: 2026-05-04T12:20:10Z
file_id: '21795'
file_name: 2026_CellReports_Vijatovic.pdf
file_size: 14925958
relation: main_file
success: 1
file_date_updated: 2026-05-04T12:20:10Z
has_accepted_license: '1'
intvolume: ' 45'
issue: '4'
language:
- iso: eng
month: '04'
oa: 1
oa_version: Published Version
pmid: 1
project:
- _id: ebb66355-77a9-11ec-83b8-b8ac210a4dae
grant_number: '101041551'
name: Development and Evolution of Tetrapod Motor Circuits
- _id: 8da85f50-16d5-11f0-9cad-eab8b0ff6c9e
grant_number: F7814
name: 'Stem Cell Modulation in Neural Development and Regeneration/ P14-Swim-to-limb
transition: cell type to connection diversity'
- _id: c08e9ad1-5a5b-11eb-8a69-9d1cf3b07473
grant_number: CZI01
name: Tools for automation and feedback microscopy
- _id: bd73af52-d553-11ed-ba76-912049f0ac7a
grant_number: FTI21-D-046
name: Development of V1 interneuron diversity during swim-to-walk transition of
Xenopus metamorphosis
publication: Cell Reports
publication_identifier:
eissn:
- 2211-1247
issn:
- 2639-1856
publication_status: published
publisher: Elsevier
quality_controlled: '1'
scopus_import: '1'
status: public
title: Multifold increase in spinal inhibitory cell types with emergence of limb movement
tmp:
image: /images/cc_by.png
legal_code_url: https://creativecommons.org/licenses/by/4.0/legalcode
name: Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)
short: CC BY (4.0)
type: journal_article
user_id: 2DF688A6-F248-11E8-B48F-1D18A9856A87
volume: 45
year: '2026'
...