The MITF paralog tfec is required in neural crest development for fate specification of the iridophore lineage from a multipotent pigment cell progenitor.
The MITF paralog tfec is required in neural crest development for fate specification of the iridophore lineage from a multipotent pigment cell progenitor.
复制标题
DOI：
10.1371/journal.pone.0244794
复制
发表时间：
2021
期刊：
影响因子：
3.7
通讯作者：
Lister JA
中科院分区：
文献类型：
--
作者：
Petratou K;Spencer SA;Kelsh RN;Lister JA
了解多能祖细胞的不同细胞类型的命运规范如何发生是胚胎学中的一个基本问题。神经嵴干细胞 (NCSC) 产生极其多样化的衍生物，包括多种神经细胞、骨骼细胞和色素细胞命运。指定 NCSC 谱系的关键转录因子和细胞外信号仍有待鉴定，而且我们对它们如何以及何时共同发挥作用以控制命运只有一点了解。斑马鱼具有三种神经嵴衍生的色素细胞类型：黑色素细胞、反光虹彩细胞和黄色黄色细胞，这为研究命运分离的分子和细胞机制提供了强大的模型。 Mitfa 已被确定为黑色素细胞命运的主要调节者。在这里，我们证明了 Mitf 相关转录因子 Tfec 作为虹膜细胞命运的主调节因子。令人惊讶的是，我们对 tfec 突变体的表型分析表明，Tfec 也在所有三种色素细胞类型的初始规范中发挥作用，尽管黑素细胞和黄色素谱系稍后恢复。我们发现 Mitfa 抑制 tfec 表达，揭示了决定黑素细胞和虹膜细胞命运的可能机制。我们的数据与长期以来提出的三能祖细胞受限于色素细胞命运的观点一致。此外，我们研究了多能 NCSC 中 tfec 的激活、维持和功能，首次证明了它在形成和维持早期神经嵴细胞的基因调控网络中的作用。总之，我们在之前的工作基础上描述了控制虹彩细胞发育的基因调控网络，将 Tfec 确立为驱动多能祖细胞虹彩细胞规范的主调控因子，同时揭示了进行性命运限制的可能细胞机制。
Understanding how fate specification of distinct cell-types from multipotent progenitors occurs is a fundamental question in embryology. Neural crest stem cells (NCSCs) generate extraordinarily diverse derivatives, including multiple neural, skeletogenic and pigment cell fates. Key transcription factors and extracellular signals specifying NCSC lineages remain to be identified, and we have only a little idea of how and when they function together to control fate. Zebrafish have three neural crest-derived pigment cell types, black melanocytes, light-reflecting iridophores and yellow xanthophores, which offer a powerful model for studying the molecular and cellular mechanisms of fate segregation. Mitfa has been identified as the master regulator of melanocyte fate. Here, we show that an Mitf-related transcription factor, Tfec, functions as master regulator of the iridophore fate. Surprisingly, our phenotypic analysis of tfec mutants demonstrates that Tfec also functions in the initial specification of all three pigment cell-types, although the melanocyte and xanthophore lineages recover later. We show that Mitfa represses tfec expression, revealing a likely mechanism contributing to the decision between melanocyte and iridophore fate. Our data are consistent with the long-standing proposal of a tripotent progenitor restricted to pigment cell fates. Moreover, we investigate activation, maintenance and function of tfec in multipotent NCSCs, demonstrating for the first time its role in the gene regulatory network forming and maintaining early neural crest cells. In summary, we build on our previous work to characterise the gene regulatory network governing iridophore development, establishing Tfec as the master regulator driving iridophore specification from multipotent progenitors, while shedding light on possible cellular mechanisms of progressive fate restriction.
登录
查看更多内容
影响因子：
2.7
作者：
D'Agati G;Beltre R;Sessa A;Burger A;Zhou Y;Mosimann C;White RM
通讯作者：
White RM
影响因子：
56.9
作者：
BAGNARA, JT;MATSUMOTO, J;TAYLOR, JD
通讯作者：
TAYLOR, JD
影响因子：
4.5
作者：
Dooley, Christopher M.;Wali, Neha;Busch-Nentwich, Elisabeth M.
通讯作者：
Busch-Nentwich, Elisabeth M.
影响因子：
3.7
作者：
Clancey, Lauren F.;Beirl, Alisha J.;Cooper, Cynthia D.
通讯作者：
Cooper, Cynthia D.
DOI：
10.1073/pnas.1308335110
发表时间：
2013-08-20
影响因子：
11.1
作者：
Jao, Li-En;Wente, Susan R.;Chen, Wenbiao
通讯作者：
Chen, Wenbiao