The Ancient Origins of Neural Substrates for Land Walking

• Published in: Cell Vol. 172; no. 4; pp. 667 - 682.e15
• Main Authors: Jung, Heekyung, Baek, Myungin, D’Elia, Kristen P., Boisvert, Catherine, Currie, Peter D., Tay, Boon-Hui, Venkatesh, Byrappa, Brown, Stuart M., Heguy, Adriana, Schoppik, David, Dasen, Jeremy S.
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 08.02.2018
• Subjects: Animal Fins - physiology; Animals; Avian Proteins - genetics; Avian Proteins - metabolism; Chick Embryo; Chickens - physiology; development; evolution; Evolution, Molecular; Fish Proteins - genetics; Fish Proteins - metabolism; Homeodomain Proteins - genetics; Homeodomain Proteins - metabolism; Hox gene; locomotion; motor neuron; Muscle, Skeletal - physiology; Nerve Net - physiology; neural circuit; Skates, Fish - physiology; spinal cord; Swimming - physiology; Transcription Factors - genetics; Transcription Factors - metabolism; Walking - physiology; Zebrafish - physiology; neural circuit; development; Hox gene; motor neuron; locomotion; spinal cord; evolution
• ISSN: 0092-8674; 1097-4172
• DOI: 10.1016/j.cell.2018.01.013

Walking is the predominant locomotor behavior expressed by land-dwelling vertebrates, but it is unknown when the neural circuits that are essential for limb control first appeared. Certain fish species display walking-like behaviors, raising the possibility that the underlying circuitry originated in primitive marine vertebrates. We show that the neural substrates of bipedalism are present in the little skate Leucoraja erinacea, whose common ancestor with tetrapods existed ∼420 million years ago. Leucoraja exhibits core features of tetrapod locomotor gaits, including left-right alternation and reciprocal extension-flexion of the pelvic fins. Leucoraja also deploys a remarkably conserved Hox transcription factor-dependent program that is essential for selective innervation of fin/limb muscle. This network encodes peripheral connectivity modules that are distinct from those used in axial muscle-based swimming and has apparently been diminished in most modern fish. These findings indicate that the circuits that are essential for walking evolved through adaptation of a genetic regulatory network shared by all vertebrates with paired appendages. [Display omitted] [Display omitted] •The little skate Leucoraja erinacea exhibits bipedal walking-like behaviors•Neuronal subtypes essential for walking originated in primitive jawed fish•Fin and limb motor neurons share a common Hox-dependent gene network•Modulation of Hox patterning facilitates evolutionary changes in MN organization The circuits involved in limb control were established in the common ancestor to all vertebrates with pair appendages millions of years before the first tetrapod walked on land.