Two T-box genes play independent and cooperative roles to regulate morphogenesis of ciliated Kupffer's vesicle in zebrafish
Two T-box genes play independent and cooperative roles to regulate morphogenesis of ciliated Kupffer's vesicle in zebrafish
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DOI：
10.1016/j.ydbio.2007.05.039
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发表时间：
2007-10-15
影响因子：
2.7
通讯作者：
Yost, H. Joseph
中科院分区：
文献类型：
--
作者：
Amack, Jeffrey D.;Wang, Xinghao;Yost, H. Joseph
大脑、心脏和胃肠道发展出明显的左右（LR）不对称。不对称纤毛依赖的流体流动在胚胎结在小鼠，Kupffer囊泡在斑马鱼，兔脊索板和胃腔顶板在青蛙似乎是一个保守的机制，指导LR不对称基因的表达，并建立器官不对称的方向。然而，控制这些基本纤毛结构形成的细胞过程和遗传途径是未知的。在斑马鱼中，迁移的背侧前体细胞（DFC）产生库普弗囊泡（KV），这是一种纤毛上皮层，形成管腔并产生流体流动。使用上皮标志物非典型蛋白激酶C（aPKC）和其他标志物来分析DFC和KV细胞，我们描述了DFC形成功能性KV的多步骤过程。使用突变体和morpholmos，我们表明，两个T盒转录因子-无尾（Ntl）/Brachyury和Tbx 16/Spadetail-合作调节DFC间充质上皮过渡（MET）和KV细胞规格的早期步骤。随后，每个转录因子独立地控制KV形成中的不同步骤：Tbx 16调节KV细胞的顶端聚集，并且Ntl是KV腔形成所必需的。通过靶向吗啉代DFCs，我们表明，这些细胞的自主功能KV形态是必要的LR图案在整个胚胎。(C)2007年由Elsevier Inc.出版
The brain, heart and gastro-intestinal tract develop distinct left-right (LR) asymmetries. Asymmetric cilia-dependent fluid flow in the embryonic node in mouse, Kupffer's vesicle in zebrafish, notochordal plate in rabbit and gastrocoel roof plate in frog appears to be a conserved mechanism that directs LR asymmetric gene expression and establishes the orientation of organ asymmetry. However, the cellular processes and genetic pathways that control the formation of these essential ciliated structures are unknown. In zebrafish, migratory dorsal forerunner cells (DFCs) give rise to Kupffer's vesicle (KV), a ciliated epithelial sheet that forms a lumen and generates fluid flow. Using the epithelial marker atypical Protein Kinase C (aPKC) and other markers to analyze DFCs and KV cells, we describe a multi-step process by which DFCs form a functional KV. Using mutants and morpholmos, we show that two T-box transcription factors-No tail (Ntl)/Brachyury and Tbx16/Spadetail-cooperatively regulate an early step of DFC mesenchyme to epithelial transition (MET) and KV cell specification. Subsequently, each transcription factor independently controls a distinct step in KV formation: Tbx16 regulates apical clustering of KV cells and Ntl is necessary for KV lumen formation. By targeting morpholinos to DFCs, we show that these cell autonomous functions in KV morphogenesis are necessary for LR patterning throughout the embryo. (C) 2007 Published by Elsevier Inc.