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Sox5 functions as a fate switch in medaka pigment cell development.

Nagao Y, Suzuki T, Shimizu A, Kimura T, Seki R, Adachi T, Inoue C, Omae Y, Kamei Y, Hara I, Taniguchi Y, Naruse K, Wakamatsu Y, Kelsh RN, Hibi M, Hashimoto H - PLoS Genet. (2014)

Bottom Line: We show that ml-3 encodes sox5, which is expressed in premigratory NCCs and differentiating xanthophores.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).

View Article: PubMed Central - PubMed

Affiliation: Division of Biological Science, Graduate School of Science, Nagoya University, Furo-cho, Chikusa-ku, Nagoya, Aichi, Japan.

ABSTRACT
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).

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Expression pattern of medaka sox5 in WT and ml-3 mutant embryos.(A, C, E, F) WT. (B, D) ml-3 mutant. (A′, B′, C″, D″) Transverse sections. (E, F) sox5 (blue) and gch (red). (A–E, E′) Lateral views. (F, F′) Dorsal views. (A) In WT embryos at 12 somite stage (12 s, 41 hpf), sox5 is expressed in premigratory NCCs (see also section in A′, black arrow) as well as in dorsal neural tube and CNS ranging from forebrain (fb) to hindbrain (hb), and in tailbud (tb). The boundary between neural tube and somite is indicated by dotted line. (B) In ml-3, the sox5 expression pattern is not markedly altered. In particular, when observed in section (B′), premigratory NCCs are positive for sox5. (C, C′, C″) At 24 somite stage (24 s, 58 hpf), sox5-expressing cells are found in dorsal neural tube, premigratory NCCs (arrows in C″) and migrating NCCs between neural tube and somite and lateral trunk surface (black arrowheads in C′, C″) pathways in WT. sox5-expressing cells scattered on lateral trunk surface are prominent in WT (C′, C″). (D, D′, D″) In ml-3, sox5 expressing cells are absent from lateral trunk surface (D′, D″), whereas sox5 expression remains in dorsal neural tube, premigratory NCCs (black arrows) and migrating NCCs between neural tube and somite (D″). Boxed portion in C, D are magnified in C′, D′, respectively. (A′, B′, C″, D″) Transverse histological section from embryos at the level as indicated by dotted line in A, B, C′ and D′. (E, E′) sox5-expressing cells on lateral trunk surfaces at 34 somite stage (34 s, 74 hpf) also express gch. White arrowhead represents an example of gch-positive sox5-expressing cell. (F, F′) On dorsal trunk surface, some sox5-negative gch-positive cells were detected (white arrows). Scale bars: (A, C) 200 µm; (C′) 100 µm; (A′, C″) 20 µm; (E) 50 µm.
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pgen-1004246-g005: Expression pattern of medaka sox5 in WT and ml-3 mutant embryos.(A, C, E, F) WT. (B, D) ml-3 mutant. (A′, B′, C″, D″) Transverse sections. (E, F) sox5 (blue) and gch (red). (A–E, E′) Lateral views. (F, F′) Dorsal views. (A) In WT embryos at 12 somite stage (12 s, 41 hpf), sox5 is expressed in premigratory NCCs (see also section in A′, black arrow) as well as in dorsal neural tube and CNS ranging from forebrain (fb) to hindbrain (hb), and in tailbud (tb). The boundary between neural tube and somite is indicated by dotted line. (B) In ml-3, the sox5 expression pattern is not markedly altered. In particular, when observed in section (B′), premigratory NCCs are positive for sox5. (C, C′, C″) At 24 somite stage (24 s, 58 hpf), sox5-expressing cells are found in dorsal neural tube, premigratory NCCs (arrows in C″) and migrating NCCs between neural tube and somite and lateral trunk surface (black arrowheads in C′, C″) pathways in WT. sox5-expressing cells scattered on lateral trunk surface are prominent in WT (C′, C″). (D, D′, D″) In ml-3, sox5 expressing cells are absent from lateral trunk surface (D′, D″), whereas sox5 expression remains in dorsal neural tube, premigratory NCCs (black arrows) and migrating NCCs between neural tube and somite (D″). Boxed portion in C, D are magnified in C′, D′, respectively. (A′, B′, C″, D″) Transverse histological section from embryos at the level as indicated by dotted line in A, B, C′ and D′. (E, E′) sox5-expressing cells on lateral trunk surfaces at 34 somite stage (34 s, 74 hpf) also express gch. White arrowhead represents an example of gch-positive sox5-expressing cell. (F, F′) On dorsal trunk surface, some sox5-negative gch-positive cells were detected (white arrows). Scale bars: (A, C) 200 µm; (C′) 100 µm; (A′, C″) 20 µm; (E) 50 µm.

Mentions: Medaka sox5 mRNA was detected throughout embryonic and early larval stages by RT-PCR (Figure S4). We used whole-mount ISH to determine the expression pattern of sox5. In WT embryos, sox5 mRNA was detected in head and tail bud regions before the onset of somite formation (data not shown). At the 12 somite stage (41 hpf), sox5 was expressed in the dorsal neural tube and premigratory NCCs (Figures 5A, 5A′). Slightly later sox5 expression was detected in migrating NCCs ventrally on a pathway between somite and neural tube (medial pathway). At 22–24 somite stage (54–58 hpf), some scattered sox5-expressing cells were observed on lateral trunk surface (Figures 5C–5C″). These signals became detectable before the onset of gch expression, but, at later stages, overlapped with that of gch in differentiating xanthophores on lateral trunk surface; in addition, a few gch-expressing sox5-negative cells were detectable on dorsal trunk surface (Figures 5E, 5E′, 5F, 5F′). We interpret these data as indicating that sox5-expressing cells on lateral trunk surface are differentiating xanthophores (xanthophore precursors), whereas leucophores (dorsal trunk cells) do not express sox5. The expression in the xanthophore lineages gradually faded after 4 dpf and became undetectable by 5 dpf. In ml-3 embryos, the sox5 expression was not significantly altered in the dorsal neural tube, premigratory NCCs, and the NCCs migrating on the medial pathway. However, the sox5-expressing cells on the lateral trunk surface were absent in ml-3 mutants (Figures 5B, 5B′, 5D–5D″). These results indicate that sox5 is expressed in the xanthophore precursors and sox5 is required exclusively for development of xanthophores.


Sox5 functions as a fate switch in medaka pigment cell development.

Nagao Y, Suzuki T, Shimizu A, Kimura T, Seki R, Adachi T, Inoue C, Omae Y, Kamei Y, Hara I, Taniguchi Y, Naruse K, Wakamatsu Y, Kelsh RN, Hibi M, Hashimoto H - PLoS Genet. (2014)

Expression pattern of medaka sox5 in WT and ml-3 mutant embryos.(A, C, E, F) WT. (B, D) ml-3 mutant. (A′, B′, C″, D″) Transverse sections. (E, F) sox5 (blue) and gch (red). (A–E, E′) Lateral views. (F, F′) Dorsal views. (A) In WT embryos at 12 somite stage (12 s, 41 hpf), sox5 is expressed in premigratory NCCs (see also section in A′, black arrow) as well as in dorsal neural tube and CNS ranging from forebrain (fb) to hindbrain (hb), and in tailbud (tb). The boundary between neural tube and somite is indicated by dotted line. (B) In ml-3, the sox5 expression pattern is not markedly altered. In particular, when observed in section (B′), premigratory NCCs are positive for sox5. (C, C′, C″) At 24 somite stage (24 s, 58 hpf), sox5-expressing cells are found in dorsal neural tube, premigratory NCCs (arrows in C″) and migrating NCCs between neural tube and somite and lateral trunk surface (black arrowheads in C′, C″) pathways in WT. sox5-expressing cells scattered on lateral trunk surface are prominent in WT (C′, C″). (D, D′, D″) In ml-3, sox5 expressing cells are absent from lateral trunk surface (D′, D″), whereas sox5 expression remains in dorsal neural tube, premigratory NCCs (black arrows) and migrating NCCs between neural tube and somite (D″). Boxed portion in C, D are magnified in C′, D′, respectively. (A′, B′, C″, D″) Transverse histological section from embryos at the level as indicated by dotted line in A, B, C′ and D′. (E, E′) sox5-expressing cells on lateral trunk surfaces at 34 somite stage (34 s, 74 hpf) also express gch. White arrowhead represents an example of gch-positive sox5-expressing cell. (F, F′) On dorsal trunk surface, some sox5-negative gch-positive cells were detected (white arrows). Scale bars: (A, C) 200 µm; (C′) 100 µm; (A′, C″) 20 µm; (E) 50 µm.
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Related In: Results  -  Collection

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pgen-1004246-g005: Expression pattern of medaka sox5 in WT and ml-3 mutant embryos.(A, C, E, F) WT. (B, D) ml-3 mutant. (A′, B′, C″, D″) Transverse sections. (E, F) sox5 (blue) and gch (red). (A–E, E′) Lateral views. (F, F′) Dorsal views. (A) In WT embryos at 12 somite stage (12 s, 41 hpf), sox5 is expressed in premigratory NCCs (see also section in A′, black arrow) as well as in dorsal neural tube and CNS ranging from forebrain (fb) to hindbrain (hb), and in tailbud (tb). The boundary between neural tube and somite is indicated by dotted line. (B) In ml-3, the sox5 expression pattern is not markedly altered. In particular, when observed in section (B′), premigratory NCCs are positive for sox5. (C, C′, C″) At 24 somite stage (24 s, 58 hpf), sox5-expressing cells are found in dorsal neural tube, premigratory NCCs (arrows in C″) and migrating NCCs between neural tube and somite and lateral trunk surface (black arrowheads in C′, C″) pathways in WT. sox5-expressing cells scattered on lateral trunk surface are prominent in WT (C′, C″). (D, D′, D″) In ml-3, sox5 expressing cells are absent from lateral trunk surface (D′, D″), whereas sox5 expression remains in dorsal neural tube, premigratory NCCs (black arrows) and migrating NCCs between neural tube and somite (D″). Boxed portion in C, D are magnified in C′, D′, respectively. (A′, B′, C″, D″) Transverse histological section from embryos at the level as indicated by dotted line in A, B, C′ and D′. (E, E′) sox5-expressing cells on lateral trunk surfaces at 34 somite stage (34 s, 74 hpf) also express gch. White arrowhead represents an example of gch-positive sox5-expressing cell. (F, F′) On dorsal trunk surface, some sox5-negative gch-positive cells were detected (white arrows). Scale bars: (A, C) 200 µm; (C′) 100 µm; (A′, C″) 20 µm; (E) 50 µm.
Mentions: Medaka sox5 mRNA was detected throughout embryonic and early larval stages by RT-PCR (Figure S4). We used whole-mount ISH to determine the expression pattern of sox5. In WT embryos, sox5 mRNA was detected in head and tail bud regions before the onset of somite formation (data not shown). At the 12 somite stage (41 hpf), sox5 was expressed in the dorsal neural tube and premigratory NCCs (Figures 5A, 5A′). Slightly later sox5 expression was detected in migrating NCCs ventrally on a pathway between somite and neural tube (medial pathway). At 22–24 somite stage (54–58 hpf), some scattered sox5-expressing cells were observed on lateral trunk surface (Figures 5C–5C″). These signals became detectable before the onset of gch expression, but, at later stages, overlapped with that of gch in differentiating xanthophores on lateral trunk surface; in addition, a few gch-expressing sox5-negative cells were detectable on dorsal trunk surface (Figures 5E, 5E′, 5F, 5F′). We interpret these data as indicating that sox5-expressing cells on lateral trunk surface are differentiating xanthophores (xanthophore precursors), whereas leucophores (dorsal trunk cells) do not express sox5. The expression in the xanthophore lineages gradually faded after 4 dpf and became undetectable by 5 dpf. In ml-3 embryos, the sox5 expression was not significantly altered in the dorsal neural tube, premigratory NCCs, and the NCCs migrating on the medial pathway. However, the sox5-expressing cells on the lateral trunk surface were absent in ml-3 mutants (Figures 5B, 5B′, 5D–5D″). These results indicate that sox5 is expressed in the xanthophore precursors and sox5 is required exclusively for development of xanthophores.

Bottom Line: We show that ml-3 encodes sox5, which is expressed in premigratory NCCs and differentiating xanthophores.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).

View Article: PubMed Central - PubMed

Affiliation: Division of Biological Science, Graduate School of Science, Nagoya University, Furo-cho, Chikusa-ku, Nagoya, Aichi, Japan.

ABSTRACT
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).

Show MeSH
Related in: MedlinePlus