Zebrafish Numb homologue: Phylogenetic evolution and involvement in regulation of left-right asymmetry
Zebrafish Numb homologue: Phylogenetic evolution and involvement in regulation of left-right asymmetry
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DOI：
10.1016/j.mod.2006.03.008
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发表时间：
2006-05-01
影响因子：
2.6
通讯作者：
Watanabe, Sumiko
中科院分区：
文献类型：
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作者：
Niikura, Yuichi;Tabata, Yoko;Watanabe, Sumiko
Numb及其同源物Numb-like（Numbl）在哺乳动物的发育中起重要作用，但在低等脊椎动物胚胎发育中的作用尚不清楚。通过检索数据库，我们克隆了一个斑马鱼的数字同源基因（znum）。znum显示与哺乳动物Numb直系同源物约60%的同一性。有趣的是，znumber缺少两个Numbl直系同源物特有的特定序列基序。然而，znumber基因的染色体定位显示与位于小鼠和人Numbl基因周围的基因共线性。此外，Numb和Numbl蛋白中保守的磷酸酪氨酸结合（PTB）结构域序列的多物种比较表明，znum与Numbl的关系比Numb更密切。znumb mRNA在多种斑马鱼成体组织中表达。在胚胎中znumber的过度表达导致发育中的心管的正常移位的缺失或逆转。此外，在znumb表达胚胎中没有观察到或观察到lefty，2的双侧转录本，这表明Notch信号传导对于斑马鱼中左右场的形成和维持是必不可少的，并且znumb通过下调内源性Notch信号传导来扰乱这一过程。(c)2006爱思唯尔爱尔兰有限公司保留所有权利。
Numb and its homologue, Numb-like (Numbl), play important roles in mammalian development, but their role in embryonic development of lower vertebrates remains unknown. We cloned a zebrafish numb homologue (znumb) by searching database. znumb shows approximately 60% identity with mammalian Numb orthologs. Interstingly, znumb lacks two specific sequence motifs unique to Numbl orthologs. However, chromosomal localization of znumb gene revealed colinearity with genes located around mouse and human Numbl genes. Furthermore, multi-species comparisons of conserved phosphotyrosine-binding (PTB) domain sequences in Numb and Numbl proteins suggest that znumb is more closely related to Numbl than Numb. znumb mRNA was expressed in a wide variety of zebrafish adult tissues. Overexpression of znumb in embryos resulted in an absence, or reversal, of the normal leftward shift of the developing heart tube. Furthermore, no or bi-lateral transcripts of lefty,2 were observed in znumb-expressing embryos, suggesting that the Notch signaling was essential for left-right field formation and maintenance in zebrafish, and that znumb perturbed this process through down-regulation of endogenous Notch signaling. (c) 2006 Elsevier Ireland Ltd. All rights reserved.