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Research article - Peer-reviewed, 2022

Hop Mice Display Synchronous Hindlimb Locomotion and a Ventrally Fused Lumbar Spinal Cord Caused by a Point Mutation in Ttc26

Bernhardt, Nadine; Memic, Fatima; Velica, Anna; Tran, Michelle A.; Vieillard, Jennifer; Sayyab, Shumaila; Chersa, Taha; Andersson, Leif; Whelan, Patrick J.; Boije, Henrik; Kullander, Klas

Abstract

Identifying the spinal circuits controlling locomotion is critical for unravelling the mechanisms controlling the production of gaits. Development of the circuits governing left-right coordination relies on axon guidance molecules such as ephrins and netrins. To date, no other class of proteins have been shown to play a role during this process. Here, we have analyzed hop mice, which walk with a characteristic hopping gait using their hindlimbs in synchrony. Fictive locomotion experiments suggest that a local defect in the ventral spinal cord contributes to the aberrant locomotor phenotype. Hop mutant spinal cords had severe morphologic defects, including the absence of the ventral midline and a poorly defined border between white and gray matter. The hop mice represent the first model where, exclusively found in the lumbar domain, the left and right components of the central pattern generators (CPGs) are fused with a synchronous hindlimb gait as a functional consequence. These defects were associated with abnormal developmental processes, including a misplaced notochord and reduced induction of ventral progenitor domains. Whereas the underlying mutation in hop mice has been suggested to lie within the Ttc26 gene, other genes in close vicinity have been associated with gait defects. Mouse embryos carrying a CRISPR replicated point mutation within Ttc26 displayed an identical morphologic phenotype. Thus, our data suggest that the assembly of the lumbar CPG network is dependent on fully functional TTC26 protein.

Keywords

central pattern generator; midline fusion; rabbit-like gait; sonic hedgehog; spinal cord; synchrony

Published in

ENeuro
2022, volume: 9, number: 2, article number: ENEURO.0518-21.2022
Publisher: SOC NEUROSCIENCE

Authors' information

Bernhardt, Nadine
Uppsala University
Bernhardt, Nadine
Technische Universitat Dresden
Memic, Fatima
Uppsala University
Velica, Anna
Uppsala University
Tran, Michelle A.
University of Calgary
Vieillard, Jennifer
Uppsala University
Sayyab, Shumaila
Swedish University of Agricultural Sciences, Department of Animal Breeding and Genetics
Chersa, Taha
University of Calgary
Andersson, Leif
Swedish University of Agricultural Sciences, Department of Animal Breeding and Genetics
Andersson, Leif
Uppsala University
Texas AandM University College Station
Whelan, Patrick J.
University of Calgary
Boije, Henrik
Uppsala University
Kullander, Klas
Uppsala University

UKÄ Subject classification

Developmental Biology
Neurosciences

Publication Identifiers

DOI: https://doi.org/10.1523/ENEURO.0518-21.2022

URI (permanent link to this page)

https://res.slu.se/id/publ/116677