The T box transcription factor no tail in ciliated cells controls zebrafish left-right asymmetry
The T box transcription factor no tail in ciliated cells controls zebrafish left-right asymmetry
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DOI：
10.1016/j.cub.2004.04.002
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发表时间：
2004-04-20
期刊：
影响因子：
9.2
通讯作者：
Yost, HJ
中科院分区：
文献类型：
--
作者：
Amack, JD;Yost, HJ
心脏、大脑和肠道形成基本的左-右不对称。在小鼠、小鸡、青蛙和斑马鱼胚胎中，专门的纤毛细胞组与LR模式有关[1]。在斑马鱼中，这些纤毛细胞存在于库普弗氏囊泡(KV)中，是背侧前体细胞(DFC)的后代[1-3]。然而，在任何脊椎动物中都没有直接证据表明参与LR发育的基因在纤毛细胞中是特定需要的。通过在斑马鱼中使用一种新的方法，我们在不影响其在胚胎其他细胞中的表达的情况下，下调了DFCs中NO尾巴(NTL，与小鼠短尾巴同源)的功能。我们发现，NTL转录因子在DFCs中自主发挥细胞功能，调节KV的形态发生和LR的确定。这是第一个证据表明基因缺失只在纤毛细胞中起作用，扰乱了脊椎动物的LR模式。我们的结果表明，纤毛KV是一种功能未知的瞬时胚胎器官，参与了斑马鱼LR发育的最早已知步骤，这表明在所有脊椎动物胚胎中，一种基于纤毛的机制建立了LR轴。
The heart, brain, and gut develop essential left-right (LR) asymmetries. Specialized groups of ciliated cells have been implicated in LR patterning in mouse, chick, frog, and zebrafish embryos [1]. In zebrafish, these ciliated cells are found in Kupffer's vesicle (KV) and are progeny of dorsal forerunner cells (DFCs) [1-3]. However, there is no direct evidence in any vertebrate that the genes involved in LR development are specifically required in ciliated cells. By using a novel method in zebrafish, we knocked down the function of no tail (ntl, homologous to mouse brachyury) in DFCs without affecting its expression in other cells in the embryo. We find that the Ntl transcription factor functions cell autonomously in DFCs to regulate KV morphogenesis and LR determination. This is the first evidence that loss-of-gene function exclusively in ciliated cells perturbs vertebrate LR patterning. Our results demonstrate that the ciliated KV, a transient embryonic organ of previously unknown function, is involved in the earliest known step in zebrafish LR development, suggesting that a ciliary-based mechanism establishes the LR axis in all vertebrate embryos.