A positive regulatory loop between foxi3a and foxi3b is essential for specification and differentiation of zebrafish epidermal ionocytes.
A positive regulatory loop between foxi3a and foxi3b is essential for specification and differentiation of zebrafish epidermal ionocytes.
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FOXI3A和FOXI3B之间的积极调节环对于斑马鱼表皮离子细胞的规范和分化至关重要。
DOI：
10.1371/journal.pone.0000302
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发表时间：
2007-03-21
期刊：
影响因子：
3.7
通讯作者：
Hwang, Pung-Pung
中科院分区：
文献类型：
--
作者：
Hsiao, Chung-Der;You, May-Su;Guh, Ying-Jey;Ma, Ming;Jiang, Yun-Jin;Hwang, Pung-Pung
表皮离子细胞在鱼类胚胎中的离子、水和酸碱平衡的跨上皮运输中起着重要作用。然而，控制表皮离子细胞特化和分化的机制仍然未知。在斑马鱼中，我们证明了Delta-Notch介导的侧抑制在从表皮干细胞中挑选出表皮离子细胞祖细胞中起着至关重要的作用。遗传突变体和变形子的整个表皮离子细胞结构域不能将DeltaC-Notch 1a/Notch 3信号从发送细胞（表皮离子细胞）传递到接收细胞（表皮干细胞），分化成表皮离子细胞。表皮离子细胞祖细胞中的低Notch活性允许激活foxi 3a和foxi 3b的翼状螺旋/叉头盒转录因子。通过获得和功能丧失的测定，我们表明，foxi 3a-foxi 3b调节环的功能作为一个主调节介导的双重作用，指定表皮离子细胞祖细胞，以及随后促进分化的Na+，K+-ATP酶丰富的细胞和H+-ATP酶丰富的细胞在浓度依赖性的方式。本研究首次为揭示低等脊椎动物表皮离子细胞特化和分化的分子机制提供了一个框架。我们提出，foxi 3a和foxi 3b之间的正调控回路不仅驱动早期的离子细胞分化，而且还防止了当foxi 3功能的主调节器单方面受损时离子细胞分化的完全阻断。
Epidermal ionocytes play essential roles in the transepithelial transportation of ions, water, and acid-base balance in fish embryos before their branchial counterparts are fully functional. However, the mechanism controlling epidermal ionocyte specification and differentiation remains unknown. In zebrafish, we demonstrated that Delta-Notch-mediated lateral inhibition plays a vital role in singling out epidermal ionocyte progenitors from epidermal stem cells. The entire epidermal ionocyte domain of genetic mutants and morphants, which failed to transmit the DeltaC-Notch1a/Notch3 signal from sending cells (epidermal ionocytes) to receiving cells (epidermal stem cells), differentiates into epidermal ionocytes. The low Notch activity in epidermal ionocyte progenitors is permissive for activating winged helix/forkhead box transcription factors of foxi3a and foxi3b. Through gain- and loss-of-function assays, we show that the foxi3a-foxi3b regulatory loop functions as a master regulator to mediate a dual role of specifying epidermal ionocyte progenitors as well as of subsequently promoting differentiation of Na+,K+-ATPase-rich cells and H+-ATPase-rich cells in a concentration-dependent manner. This study provides a framework to show the molecular mechanism controlling epidermal ionocyte specification and differentiation in a low vertebrate for the first time. We propose that the positive regulatory loop between foxi3a and foxi3b not only drives early ionocyte differentiation but also prevents the complete blockage of ionocyte differentiation when the master regulator of foxi3 function is unilaterally compromised.
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