title: Doublecortin marks a new population of transiently amplifying muscle progenitor cells and is required for myofiber maturation during skeletal muscle regeneration.
abstract: Muscle satellite cells are indispensable for muscle regeneration, but the functional diversity of their daughter cells is unknown. Here, we show that many Pax7(+)MyoD(-) cells locate both beneath and outside the basal lamina during myofiber maturation. A large majority of these Pax7(+)MyoD(-) cells are not self-renewed satellite cells, but have different potentials for both proliferation and differentiation from Pax7(+)MyoD(+) myoblasts (classical daughter cells), and are specifically marked by expression of the doublecortin (Dcx) gene. Transplantation and lineage-tracing experiments demonstrated that Dcx-expressing cells originate from quiescent satellite cells and that the microenvironment induces Dcx in myoblasts. Expression of Dcx seems to be necessary for myofiber maturation because Dcx-deficient mice exhibited impaired myofiber maturation resulting from a decrease in the number of myonuclei. Furthermore, in vitro and in vivo studies suggest that one function of Dcx in myogenic cells is acceleration of cell motility. These results indicate that Dcx is a new marker for the Pax7(+)MyoD(-) subpopulation, which contributes to myofiber maturation during muscle regeneration.
authors.affiliation: Laboratory of Molecular and Cellular Physiology, Graduate School of Pharmaceutical Sciences, Osaka University, 1-6 Yamada-oka, Suita, Osaka 565-0871, Japan.
authors.forename: Ryo
authors.initials: R
authors.lastname: Ogawa
authors.affiliation: Laboratory of Molecular and Cellular Physiology, Graduate School of Pharmaceutical Sciences, Osaka University, 1-6 Yamada-oka, Suita, Osaka 565-0871, Japan.
authors.forename: Yuran
authors.initials: Y
authors.lastname: Ma
authors.affiliation: Laboratory of Molecular and Cellular Physiology, Graduate School of Pharmaceutical Sciences, Osaka University, 1-6 Yamada-oka, Suita, Osaka 565-0871, Japan.
authors.forename: Masahiko
authors.initials: M
authors.lastname: Yamaguchi
authors.affiliation: Laboratory of Molecular and Cellular Physiology, Graduate School of Pharmaceutical Sciences, Osaka University, 1-6 Yamada-oka, Suita, Osaka 565-0871, Japan.
authors.forename: Takahito
authors.initials: T
authors.lastname: Ito
authors.affiliation: Laboratory of Molecular and Cellular Physiology, Graduate School of Pharmaceutical Sciences, Osaka University, 1-6 Yamada-oka, Suita, Osaka 565-0871, Japan.
authors.forename: Yoko
authors.initials: Y
authors.lastname: Watanabe
authors.affiliation: Laboratory of Molecular and Cellular Physiology, Graduate School of Pharmaceutical Sciences, Osaka University, 1-6 Yamada-oka, Suita, Osaka 565-0871, Japan.
authors.forename: Takuji
authors.initials: T
authors.lastname: Ohtani
authors.affiliation: Laboratory of Molecular and Cellular Physiology, Graduate School of Pharmaceutical Sciences, Osaka University, 1-6 Yamada-oka, Suita, Osaka 565-0871, Japan.
authors.forename: Satoshi
authors.initials: S
authors.lastname: Murakami
authors.affiliation: Institute of Cardiovascular Regeneration, Centre for Molecular Medicine, Goethe University Frankfurt, Theodor-Stern-Kai 7, Frankfurt am Main 60590, Germany.
authors.forename: Shizuka
authors.initials: S
authors.lastname: Uchida
authors.affiliation: Max Planck Institute for Heart and Lung Research, Ludwigstrasse 43, Bad Nauheim 61231, Germany.
authors.forename: Piera
authors.initials: P
authors.lastname: De Gaspari
authors.affiliation: Division for Therapies Against Intractable Diseases, Institute for Comprehensive Medical Science, Fujita Health University, 1-98 Dengakugakubo, Kutsukake, Toyoake, Aichi 470-1192, Japan.
authors.forename: Akiyoshi
authors.initials: A
authors.lastname: Uezumi
authors.affiliation: Laboratory of Molecular and Cellular Physiology, Graduate School of Pharmaceutical Sciences, Osaka University, 1-6 Yamada-oka, Suita, Osaka 565-0871, Japan.
authors.forename: Miki
authors.initials: M
authors.lastname: Nakamura
authors.affiliation: Department of Molecular Therapy, National Institute of Neuroscience, National Center of Neurology and Psychiatry, 4-1-1 Ogawa-higashi, Kodaira, Tokyo 187-8502, Japan.
authors.forename: Yuko
authors.initials: Y
authors.lastname: Miyagoe-Suzuki
authors.affiliation: Laboratory of Molecular and Cellular Physiology, Graduate School of Pharmaceutical Sciences, Osaka University, 1-6 Yamada-oka, Suita, Osaka 565-0871, Japan.
authors.forename: Kazutake
authors.initials: K
authors.lastname: Tsujikawa
authors.affiliation: Department of Regenerative Medicine, National Institute for Longevity Sciences, National Center for Geriatrics and Gerontology, 35 Gengo, Morioka, Oobu, Aichi 474-8522, Japan.
authors.forename: Naohiro
authors.initials: N
authors.lastname: Hashimoto
authors.affiliation: Max Planck Institute for Heart and Lung Research, Ludwigstrasse 43, Bad Nauheim 61231, Germany.
authors.forename: Thomas
authors.initials: T
authors.lastname: Braun
authors.affiliation: Department of Developmental Medical Sciences, Graduate School of Medicine, University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-0033, Japan.
authors.forename: Teruyuki
authors.initials: T
authors.lastname: Tanaka
authors.affiliation: Department of Molecular Therapy, National Institute of Neuroscience, National Center of Neurology and Psychiatry, 4-1-1 Ogawa-higashi, Kodaira, Tokyo 187-8502, Japan.
authors.forename: Shin'ichi
authors.initials: S
authors.lastname: Takeda
authors.affiliation: Laboratory of Molecular and Cellular Physiology, Graduate School of Pharmaceutical Sciences, Osaka University, 1-6 Yamada-oka, Suita, Osaka 565-0871, Japan.
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Yamamoto
authors.affiliation: Laboratory of Molecular and Cellular Physiology, Graduate School of Pharmaceutical Sciences, Osaka University, 1-6 Yamada-oka, Suita, Osaka 565-0871, Japan fukada@phs.osaka-u.ac.jp.
authors.forename: So-Ichiro
authors.initials: S
authors.lastname: Fukada
mesh_terms: D000818:Animals; D054715:Cardiotoxins / Q000008:administration & dosage; D002454:Cell Differentiation; D002465:Cell Movement; D060833:Cellular Microenvironment; D000089622:Doublecortin Domain Proteins; D000089662:Doublecortin Protein; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008869:Microtubule-Associated Proteins / Q000172:deficiency / Q000378:metabolism*; D018485:Muscle Fibers, Skeletal / Q000166:cytology* / Q000502:physiology*; D017570:MyoD Protein / Q000378:metabolism; D032446:Myoblasts / Q000166:cytology / Q000378:metabolism; D009479:Neuropeptides / Q000172:deficiency / Q000378:metabolism*; D051763:PAX7 Transcription Factor / Q000378:metabolism; D012038:Regeneration / Q000502:physiology*; D032496:Satellite Cells, Skeletal Muscle / Q000166:cytology; D013234:Stem Cells / Q000166:cytology* / Q000378:metabolism
chemical_list: D054715:Cardiotoxins; C000714847:Dcx protein, mouse; D000089622:Doublecortin Domain Proteins; D000089662:Doublecortin Protein; D008869:Microtubule-Associated Proteins; D017570:MyoD Protein; D009479:Neuropeptides; D051763:PAX7 Transcription Factor; C497322:Pax7 protein, mouse
keywords: Doublecortin; Myofiber maturation; Regeneration; Satellite cells