TY - JOUR
T1 - Control of species-dependent cortico-motoneuronal connections underlying manual dexterity
AU - Gu, Zirong
AU - Kalamboglas, John
AU - Yoshioka, Shin
AU - Han, Wenqi
AU - Li, Zhuo
AU - Kawasawa, Yuka Imamura
AU - Pochareddy, Sirisha
AU - Li, Zhen
AU - Liu, Fuchen
AU - Xu, Xuming
AU - Wijeratne, Sagara
AU - Ueno, Masaki
AU - Blatz, Emily
AU - Salomone, Joseph
AU - Kumanogoh, Atsushi
AU - Rasin, Mladen Roko
AU - Gebelein, Brian
AU - Weirauch, Matthew T.
AU - Sestan, Nenad
AU - Martin, John H.
AU - Yoshida, Yutaka
N1 - Funding Information:
We are grateful to M. Baccei, J. N. Betley, K. Campbell, S. Crone, C. Gu, T. Isa, D. Ladle, M. Nakafuku, and R. Yu for critical comments on the manuscript. We thank Boston Children?s Hospital Viral Core (supported by core grant NEI 5P30EY012196-17) for making the AAV6-G virus. We thank P. Arlotta for the Fezf2 construct. Z.G. and E.B. were supported by the Graduate Summer Undergraduate Mentoring Program at the University of Cincinnati. M.T.W. is supported by the National Institutes of Health (NIH) grants R01 NS099068 and R21 HG008186, Lupus Research Alliance ?Novel Approaches? award, and a CCHMC CpG Pilot Study award. N.S. is supported by NIH grants MH106934 and MH103339. J.H.M. and Y.Y. are supported by NIH grants NS079569 and NS093002, respectively. All data are available in the main texts and supplementary materials. Z.G. and Y.Y. conceived of the project and contributed to experimental design and interpretation. Z.G. performed most of the experiments. Z.G., J.K., and J.H.M. designed the cortico-muscular electrophysiology assay, performed EMG recordings, and analyzed and interpreted the electrophysiological data. Y.I.K., W.H., Z.L., Z.L., F.L., S.P., X.X., and N.S. performed the in situ hybridizations using human tissues, chromatin immunoprecipitation?sequencing using human and mouse tissues, and culture experiments using Fezf2-floxed mice. S.Y. contributed to cloning of the human and mouse genomic regions and the luciferase assays. E.B. performed the grid-walking test and contributed to the immunochemistry studies. M.U. purified rabies viruses and assisted in the dorsal hemisection surgery. S.W. and M.-R.R. analyzed the cortical layers and cortico-cortical projections and also conducted the Golgi analyses. J.S. and B.G. performed the EMSA analyses. M.T.W. performed the cross-species cis-regulatory element comparisons. A.K. provided the Sema6D mutant mice. Y.Y. supervised all aspects of the work, and Z.G., J.H.M, and Y.Y. prepared the manuscript with contributions from other authors.
PY - 2017/7/28
Y1 - 2017/7/28
N2 - Superior manual dexterity in higher primates emerged together with the appearance of cortico-motoneuronal (CM) connections during the evolution of the mammalian corticospinal (CS) system. Previously thought to be specific to higher primates, we identified transient CM connections in early postnatal mice, which are eventually eliminated by Sema6D-PlexA1 signaling. PlexA1 mutant mice maintain CM connections into adulthood and exhibit superior manual dexterity as compared with that of controls. Last, differing PlexA1 expression in layer 5 of the motor cortex, which is strong in wild-type mice but weak in humans, may be explained by FEZF2-mediated cis-regulatory elements that are found only in higher primates. Thus, species-dependent regulation of PlexA1 expression may have been crucial in the evolution of mammalian CS systems that improved fine motor control in higher primates.
AB - Superior manual dexterity in higher primates emerged together with the appearance of cortico-motoneuronal (CM) connections during the evolution of the mammalian corticospinal (CS) system. Previously thought to be specific to higher primates, we identified transient CM connections in early postnatal mice, which are eventually eliminated by Sema6D-PlexA1 signaling. PlexA1 mutant mice maintain CM connections into adulthood and exhibit superior manual dexterity as compared with that of controls. Last, differing PlexA1 expression in layer 5 of the motor cortex, which is strong in wild-type mice but weak in humans, may be explained by FEZF2-mediated cis-regulatory elements that are found only in higher primates. Thus, species-dependent regulation of PlexA1 expression may have been crucial in the evolution of mammalian CS systems that improved fine motor control in higher primates.
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U2 - 10.1126/science.aan3721
DO - 10.1126/science.aan3721
M3 - Article
C2 - 28751609
AN - SCOPUS:85026321771
VL - 357
SP - 400
EP - 404
JO - Science
JF - Science
SN - 0036-8075
IS - 6349
ER -