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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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Dual expression of sox5 and pax7a is required for xanthophore development.(A, B) gch. (C–E, I′) pax7a. (F, G, H′) sox5. (A, F) lf mutant. (B, E, G) lf-2 mutant. (C, H, I) WT. (D) ml-3 mutant. (A–G) Lateral views. (H, I) Dorsal views. (C′, C″, D′, D″, E′, F′, G′) Transverse section. (A, B) gch expression in lf and lf-2 at 34 somite stage (34 s, 74 hpf). gch is normally expressed in lf (A), whereas in lf-2 gch-expressing cells are completely absent (B). (C–E) pax7a expression in WT, ml-3 and lf-2 at 24 somite stage (24 s, 58 hpf). In WT, pax7a is expressed in dorsal neural tube, premigratory NCCs (black arrows) in migratory NCCs between neural tube and somite and on lateral trunk surface (black arrowheads, C–C″). In ml-3, pax7a-expressing cells are lost from lateral trunk surface (D–D″). In lf-2, pax7a expression in premigratory and migratory NCCs was absent (E, E′). (F, G) sox5 expression in lf and lf-2 at 24 s. sox5 expression is normal in lf being detected in dorsal neural tube, premigratory NCCs (black arrows) and migrating NCCs between neural tube and somite and on lateral trunk surface (black arrowheads) as in WT (F, F′). In lf-2, premigratory NCC expression remains detectable, but sox5-expressing cells are lost from lateral trunk surface (G, G′). (E′–G′) The histological section from embryos at the level as indicated by dotted line in E, F and G. (C′, C″, D′, D″) Transverse sections from embryos were selected from the region boxed by dotted line in C and D. (H, I) Expression of sox5 and pax7a on dorsal trunk surface in WT at 90 hpf. (H, I) Pre-fixed WT embryos in bright field. The same embryos were processed for sox5 (H′) and pax7a (I′) ISH. Leucophores are positive for pax7a expression (I′, compare white arrowhead positions with I) but not for sox5 expression (H′). Scale bars: (A, C, E) 200 µm; (C′, E′) 20 µm; (G) 50 µm.
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pgen-1004246-g007: Dual expression of sox5 and pax7a is required for xanthophore development.(A, B) gch. (C–E, I′) pax7a. (F, G, H′) sox5. (A, F) lf mutant. (B, E, G) lf-2 mutant. (C, H, I) WT. (D) ml-3 mutant. (A–G) Lateral views. (H, I) Dorsal views. (C′, C″, D′, D″, E′, F′, G′) Transverse section. (A, B) gch expression in lf and lf-2 at 34 somite stage (34 s, 74 hpf). gch is normally expressed in lf (A), whereas in lf-2 gch-expressing cells are completely absent (B). (C–E) pax7a expression in WT, ml-3 and lf-2 at 24 somite stage (24 s, 58 hpf). In WT, pax7a is expressed in dorsal neural tube, premigratory NCCs (black arrows) in migratory NCCs between neural tube and somite and on lateral trunk surface (black arrowheads, C–C″). In ml-3, pax7a-expressing cells are lost from lateral trunk surface (D–D″). In lf-2, pax7a expression in premigratory and migratory NCCs was absent (E, E′). (F, G) sox5 expression in lf and lf-2 at 24 s. sox5 expression is normal in lf being detected in dorsal neural tube, premigratory NCCs (black arrows) and migrating NCCs between neural tube and somite and on lateral trunk surface (black arrowheads) as in WT (F, F′). In lf-2, premigratory NCC expression remains detectable, but sox5-expressing cells are lost from lateral trunk surface (G, G′). (E′–G′) The histological section from embryos at the level as indicated by dotted line in E, F and G. (C′, C″, D′, D″) Transverse sections from embryos were selected from the region boxed by dotted line in C and D. (H, I) Expression of sox5 and pax7a on dorsal trunk surface in WT at 90 hpf. (H, I) Pre-fixed WT embryos in bright field. The same embryos were processed for sox5 (H′) and pax7a (I′) ISH. Leucophores are positive for pax7a expression (I′, compare white arrowhead positions with I) but not for sox5 expression (H′). Scale bars: (A, C, E) 200 µm; (C′, E′) 20 µm; (G) 50 µm.

Mentions: To begin to reveal the gene cascade underlying specification of xanthophore and leucophore lineages, we examined lf (slc2a15b) and lf-2 (pax7a) mutant embryos (Kimura et al, unpublished data), which each lacks discernible xanthophores and leucophores except for occasional escaper leucophores in lf-2[30], [31]. gch expression was normal in lf but was absent in lf-2 at 34 somite stage (Figures 7A, 7B). This is consistent with our previous findings that slc2a15b is required for pigmentation of xanthophores and leucophores, whereas pax7a is required for specification of both xanthophore and leucophore lineages. We next examined the expression of pax7a (AB827303) in ml-3 and lf-2 mutants, and the expression of sox5 in lf and lf-2 mutants. Similar to sox5, pax7a was detected in the dorsal neural tube, premigratory NCCs, and migrating NCCs on the trunk surface in WT (Figures 7C–7C″). We found that pax7a was expressed in both differentiating xanthophores and leucophores, whereas sox5 expression was not detected in early leucophores (Figures 7C, 7C′, 7H, 7H′, 7I, 7I′). pax7a expression was absent in cells on the lateral trunk surface in ml-3 mutants (Figures 7D, 7D′), suggesting that the absence of pax7a on the trunk surface in ml-3 mutants reflects the absence of the xanthophore lineage. The pax7a-expressing premigratory NCCs were not altered in ml-3 mutants (Figure 7D″), whereas lf-2 mutants lack both of pax7a-expressing premigratory NCCs and differentiating xanthophores (Figures 7E, 7E′), suggesting that pax7a-positive premigratory NCCs are a shared precursor for both xanthophores and leucophores (shared xanthophore-leucophore progenitor).


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)

Dual expression of sox5 and pax7a is required for xanthophore development.(A, B) gch. (C–E, I′) pax7a. (F, G, H′) sox5. (A, F) lf mutant. (B, E, G) lf-2 mutant. (C, H, I) WT. (D) ml-3 mutant. (A–G) Lateral views. (H, I) Dorsal views. (C′, C″, D′, D″, E′, F′, G′) Transverse section. (A, B) gch expression in lf and lf-2 at 34 somite stage (34 s, 74 hpf). gch is normally expressed in lf (A), whereas in lf-2 gch-expressing cells are completely absent (B). (C–E) pax7a expression in WT, ml-3 and lf-2 at 24 somite stage (24 s, 58 hpf). In WT, pax7a is expressed in dorsal neural tube, premigratory NCCs (black arrows) in migratory NCCs between neural tube and somite and on lateral trunk surface (black arrowheads, C–C″). In ml-3, pax7a-expressing cells are lost from lateral trunk surface (D–D″). In lf-2, pax7a expression in premigratory and migratory NCCs was absent (E, E′). (F, G) sox5 expression in lf and lf-2 at 24 s. sox5 expression is normal in lf being detected in dorsal neural tube, premigratory NCCs (black arrows) and migrating NCCs between neural tube and somite and on lateral trunk surface (black arrowheads) as in WT (F, F′). In lf-2, premigratory NCC expression remains detectable, but sox5-expressing cells are lost from lateral trunk surface (G, G′). (E′–G′) The histological section from embryos at the level as indicated by dotted line in E, F and G. (C′, C″, D′, D″) Transverse sections from embryos were selected from the region boxed by dotted line in C and D. (H, I) Expression of sox5 and pax7a on dorsal trunk surface in WT at 90 hpf. (H, I) Pre-fixed WT embryos in bright field. The same embryos were processed for sox5 (H′) and pax7a (I′) ISH. Leucophores are positive for pax7a expression (I′, compare white arrowhead positions with I) but not for sox5 expression (H′). Scale bars: (A, C, E) 200 µm; (C′, E′) 20 µm; (G) 50 µm.
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pgen-1004246-g007: Dual expression of sox5 and pax7a is required for xanthophore development.(A, B) gch. (C–E, I′) pax7a. (F, G, H′) sox5. (A, F) lf mutant. (B, E, G) lf-2 mutant. (C, H, I) WT. (D) ml-3 mutant. (A–G) Lateral views. (H, I) Dorsal views. (C′, C″, D′, D″, E′, F′, G′) Transverse section. (A, B) gch expression in lf and lf-2 at 34 somite stage (34 s, 74 hpf). gch is normally expressed in lf (A), whereas in lf-2 gch-expressing cells are completely absent (B). (C–E) pax7a expression in WT, ml-3 and lf-2 at 24 somite stage (24 s, 58 hpf). In WT, pax7a is expressed in dorsal neural tube, premigratory NCCs (black arrows) in migratory NCCs between neural tube and somite and on lateral trunk surface (black arrowheads, C–C″). In ml-3, pax7a-expressing cells are lost from lateral trunk surface (D–D″). In lf-2, pax7a expression in premigratory and migratory NCCs was absent (E, E′). (F, G) sox5 expression in lf and lf-2 at 24 s. sox5 expression is normal in lf being detected in dorsal neural tube, premigratory NCCs (black arrows) and migrating NCCs between neural tube and somite and on lateral trunk surface (black arrowheads) as in WT (F, F′). In lf-2, premigratory NCC expression remains detectable, but sox5-expressing cells are lost from lateral trunk surface (G, G′). (E′–G′) The histological section from embryos at the level as indicated by dotted line in E, F and G. (C′, C″, D′, D″) Transverse sections from embryos were selected from the region boxed by dotted line in C and D. (H, I) Expression of sox5 and pax7a on dorsal trunk surface in WT at 90 hpf. (H, I) Pre-fixed WT embryos in bright field. The same embryos were processed for sox5 (H′) and pax7a (I′) ISH. Leucophores are positive for pax7a expression (I′, compare white arrowhead positions with I) but not for sox5 expression (H′). Scale bars: (A, C, E) 200 µm; (C′, E′) 20 µm; (G) 50 µm.
Mentions: To begin to reveal the gene cascade underlying specification of xanthophore and leucophore lineages, we examined lf (slc2a15b) and lf-2 (pax7a) mutant embryos (Kimura et al, unpublished data), which each lacks discernible xanthophores and leucophores except for occasional escaper leucophores in lf-2[30], [31]. gch expression was normal in lf but was absent in lf-2 at 34 somite stage (Figures 7A, 7B). This is consistent with our previous findings that slc2a15b is required for pigmentation of xanthophores and leucophores, whereas pax7a is required for specification of both xanthophore and leucophore lineages. We next examined the expression of pax7a (AB827303) in ml-3 and lf-2 mutants, and the expression of sox5 in lf and lf-2 mutants. Similar to sox5, pax7a was detected in the dorsal neural tube, premigratory NCCs, and migrating NCCs on the trunk surface in WT (Figures 7C–7C″). We found that pax7a was expressed in both differentiating xanthophores and leucophores, whereas sox5 expression was not detected in early leucophores (Figures 7C, 7C′, 7H, 7H′, 7I, 7I′). pax7a expression was absent in cells on the lateral trunk surface in ml-3 mutants (Figures 7D, 7D′), suggesting that the absence of pax7a on the trunk surface in ml-3 mutants reflects the absence of the xanthophore lineage. The pax7a-expressing premigratory NCCs were not altered in ml-3 mutants (Figure 7D″), whereas lf-2 mutants lack both of pax7a-expressing premigratory NCCs and differentiating xanthophores (Figures 7E, 7E′), suggesting that pax7a-positive premigratory NCCs are a shared precursor for both xanthophores and leucophores (shared xanthophore-leucophore progenitor).

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