Sox5 functions as a fate switch in medaka pigment cell development.
Mechanisms generating diverse cell types from multipotent progenitors are crucial for normal development. Neural crest cells (NCCs) are multipotent stem cells that give rise to numerous cell-types, including pigment cells. Medaka has four types of NCC-derived pigment cells (xanthophores, leucophores, melanophores and iridophores), making medaka pigment cell development an excellent model for studying the mechanisms controlling specification of distinct cell types from a multipotent progenitor. Medaka many leucophores-3 (ml-3) mutant embryos exhibit a unique phenotype characterized by excessive formation of leucophores and absence of xanthophores. We show that ml-3 encodes sox5, which is expressed in premigratory NCCs and differentiating xanthophores. Cell transplantation studies reveal a cell-autonomous role of sox5 in the xanthophore lineage. pax7a is expressed in NCCs and required for both xanthophore and leucophore lineages; we demonstrate that Sox5 functions downstream of Pax7a. We propose a model in which multipotent NCCs first give rise to pax7a-positive partially fate-restricted intermediate progenitors for xanthophores and leucophores; some of these progenitors then express sox5, and as a result of Sox5 action develop into xanthophores. Our results provide the first demonstration that Sox5 can function as a molecular switch driving specification of a specific cell-fate (xanthophore) from a partially-restricted, but still multipotent, progenitor (the shared xanthophore-leucophore progenitor).
Division of Biological Science, Graduate School of Science, Nagoya University, Furo-cho, Chikusa-ku, Nagoya, Aichi, Japan.
Yusuke
Y
Nagao
Division of Biological Science, Graduate School of Science, Nagoya University, Furo-cho, Chikusa-ku, Nagoya, Aichi, Japan.
Takao
T
Suzuki
Division of Biomedical Information Analysis, Iwate Tohoku Medical Megabank Organization, Iwate Medical University, Yahaba-cho, Shiwa-gun, Iwate, Japan.
Atsushi
A
Shimizu
National Institute for Basic Biology, Interuniversity Bio-Backup Project Center, Okazaki, Aichi, Japan; Department of Basic Biology, School of Life Science, The Graduate University for Advanced Studies (SOKENDAI), Myodaiji, Okazaki, Aichi, Japan.
Tetsuaki
T
Kimura
Bioscience and Biotechnology Center, Nagoya University, Furo-cho, Chikusa-ku, Nagoya, Aichi, Japan.
Ryoko
R
Seki
Bioscience and Biotechnology Center, Nagoya University, Furo-cho, Chikusa-ku, Nagoya, Aichi, Japan; Centre for Regenerative Medicine and Department of Biology and Biochemistry, University of Bath, Bath, Claverton Down, United Kingdom.
Tomoko
T
Adachi
Bioscience and Biotechnology Center, Nagoya University, Furo-cho, Chikusa-ku, Nagoya, Aichi, Japan.
Chikako
C
Inoue
Division of Biological Science, Graduate School of Science, Nagoya University, Furo-cho, Chikusa-ku, Nagoya, Aichi, Japan.
Yoshihiro
Y
Omae
Department of Basic Biology, School of Life Science, The Graduate University for Advanced Studies (SOKENDAI), Myodaiji, Okazaki, Aichi, Japan; Spectrography and Bioimaging Facility, National Institute for Basic Biology, Myodaiji, Okazaki, Aichi, Japan.
Yasuhiro
Y
Kamei
Laboratory of Bioresources, National Institute for Basic Biology, Myodaiji, Okazaki, Aichi, Japan.
Ikuyo
I
Hara
Department of Preventive Medicine and Public Health, School of Medicine, Keio University, Shinjuku-ku, Tokyo, Japan.
Yoshihito
Y
Taniguchi
National Institute for Basic Biology, Interuniversity Bio-Backup Project Center, Okazaki, Aichi, Japan; Department of Basic Biology, School of Life Science, The Graduate University for Advanced Studies (SOKENDAI), Myodaiji, Okazaki, Aichi, Japan; Laboratory of Bioresources, National Institute for Basic Biology, Myodaiji, Okazaki, Aichi, Japan.
Kiyoshi
K
Naruse
Division of Biological Science, Graduate School of Science, Nagoya University, Furo-cho, Chikusa-ku, Nagoya, Aichi, Japan; Bioscience and Biotechnology Center, Nagoya University, Furo-cho, Chikusa-ku, Nagoya, Aichi, Japan.
Yuko
Y
Wakamatsu
Centre for Regenerative Medicine and Department of Biology and Biochemistry, University of Bath, Bath, Claverton Down, United Kingdom.
Robert N
RN
Kelsh
Division of Biological Science, Graduate School of Science, Nagoya University, Furo-cho, Chikusa-ku, Nagoya, Aichi, Japan; Bioscience and Biotechnology Center, Nagoya University, Furo-cho, Chikusa-ku, Nagoya, Aichi, Japan.
Masahiko
M
Hibi
Division of Biological Science, Graduate School of Science, Nagoya University, Furo-cho, Chikusa-ku, Nagoya, Aichi, Japan; Bioscience and Biotechnology Center, Nagoya University, Furo-cho, Chikusa-ku, Nagoya, Aichi, Japan.
Hisashi
H
Hashimoto
D000818:Animals; D002454:Cell Differentiation / Q000235:genetics / Q000502:physiology; D029941:Fish Proteins / Q000235:genetics; D018507:Gene Expression Regulation, Developmental / Q000235:genetics; D008547:Melanophores / Q000502:physiology; D009432:Neural Crest / Q000254:growth & development* / Q000502:physiology; D009990:Oryzias / Q000254:growth & development* / Q000502:physiology; D051763:PAX7 Transcription Factor / Q000235:genetics; D010641:Phenotype; D010858:Pigmentation / Q000235:genetics* / Q000502:physiology; D055755:SOXD Transcription Factors / Q000235:genetics*; D013234:Stem Cells / Q000502:physiology
D029941:Fish Proteins; D051763:PAX7 Transcription Factor; D055755:SOXD Transcription Factors