Sox5 functions as a fate switch in medaka pigment cell development.
Sox5 functions as a fate switch in medaka pigment cell development.
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DOI：
10.1371/journal.pgen.1004246
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发表时间：
2014-04
期刊：
影响因子：
4.5
通讯作者：
Hashimoto H
中科院分区：
文献类型：
--
作者：
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
从多能祖细胞产生不同类型的细胞的机制对正常发育至关重要。神经脊细胞(NCC)是一种多能干细胞，可产生包括色素细胞在内的多种细胞类型。青竹拥有四种由NCC衍生的色素细胞(黄色素细胞、白血色素细胞、黑色素细胞和虹膜细胞)，这使得青竹色素细胞的发展成为研究控制多能祖细胞不同细胞类型规格的机制的极佳模型。许多亮黄素-3(ml-3)突变胚胎表现出一种独特的表型，其特征是过量形成亮色团，而缺乏黄素团。我们发现，m1-3编码sox5，它在迁移前的NCC和分化的黄原细胞中表达。细胞移植研究揭示了Sox5在叶黄菌谱系中的细胞自主作用。Pax7a在NCC中表达，对黄体和白细胞系都是必需的；我们证明了Sox5在Pax7a下游发挥作用。我们提出了一个模型，在这个模型中，多能NCC首先产生部分命运受限的pax7a阳性的黄磷和利血磷中间前体，其中一些表达Sox5，并作为Sox5作用的结果发展成黄磷。我们的结果第一次证明了Sox5可以作为分子开关来驱动特定细胞命运(叶黄原)的规范，来自部分受限但仍然多能的前体(共享的叶黄原-利血原)。如何从多能祖细胞中确定单个细胞的命运是发育和干细胞生物学中的一个基本问题。越来越多的证据表明，干细胞在通过一个或多个部分受限的中间体后，会发育成每一种最终的、不同的细胞类型，但最终命运选择背后的分子机制在很大程度上是未知的。神经脊细胞(NCC)具有多种细胞类型，包括多种色素细胞，是理解FATE调控机制的理想模型。我们研究了青竹中部分受限的色素细胞祖细胞是如何做出特定命运选择的。我们发现，Sry相关的转录因子Sox5在决定黄色素团和白色素团之间的命运时是必需的，它的缺失导致了亮色团的过度形成和黄素体的缺失。我们证明了Sox5在青竹的叶黄团谱系中的细胞自主功能。此外，pax7a在部分受限的祖细胞中表达，这些祖细胞与叶黄体和白细胞系共有，而Sox5在这些细胞中的一些细胞中作用于促进叶黄体谱系。我们的工作揭示了Sox5作为一个分子开关的作用，决定了共同祖先对叶黄团和利色团命运的选择，并确定了从NCC中调节色素细胞命运选择的重要机制。
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). How individual cell fates are specified from multipotent progenitor cells is a fundamental question in developmental and stem cell biology. Accumulating evidence indicates that stem cells develop into each of their final, diverse cell-types after progression through one or more partially-restricted intermediates, but the molecular mechanisms underlying final fate choice are largely unknown. Neural crest cells (NCCs) give rise to diverse cell-types including multiple pigment cells and thus are a favored model for understanding the mechanism of fate specification. We have investigated how a specific fate choice is made from partially-restricted pigment cell progenitors in medaka. We show that Sry-related transcription factor Sox5 is required for fate determination between yellow xanthophore and white leucophore, and its loss causes excessive formation of leucophores and absence of xanthophores. We demonstrate that Sox5 functions cell-autonomously in the xanthophore lineage in medaka. Furthermore, pax7a is expressed in the partially-restricted progenitor cells shared with xanthophore and leucophore lineages, and Sox5 acts in some of these cells to promote xanthophore lineage. Our work reveals the role of Sox5 as a molecular switch determining xanthophore versus leucophore fate choice from the shared progenitor, and identifies an important mechanism regulating pigment cell fate choice from NCCs.
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影响因子：
3.5
作者：
Bondurand, N;Pingault, V;Goossens, M
通讯作者：
Goossens, M
DOI：
10.1073/pnas.28.10.396
发表时间：
1942-01-01
影响因子：
11.1
作者：
Fries, EFB
通讯作者：
Fries, EFB
影响因子：
2.7
作者：
Ignatius, Myron S.;Moose, Holly E.;Henion, Paul D.
通讯作者：
Henion, Paul D.
影响因子：
64.5
作者：
HODGKINSON, CA;MOORE, KJ;ARNHEITER, H
通讯作者：
ARNHEITER, H
影响因子：
2.6
作者：
Kimura, T;Jindo, T;Takeda, H
通讯作者：
Takeda, H