Niikura Yuichi, Tabata Yoko, Tajima Atsushi, Inoue Ituro, Arai Ken-ichi, Watanabe Sumiko
Department of Molecular and Developmental Biology, Institute of Medical Science, University of Tokyo, 4-6-1 Shirokanedai, Minato-ku, Tokyo 108-8639, Japan.
Mech Dev. 2006 May;123(5):407-14. doi: 10.1016/j.mod.2006.03.008. Epub 2006 May 15.
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 lefty2 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.
麻木蛋白及其同源物类麻木蛋白（Numbl）在哺乳动物发育过程中发挥着重要作用，但其在低等脊椎动物胚胎发育中的作用仍不清楚。我们通过搜索数据库克隆了斑马鱼的麻木蛋白同源物（znumb）。znumb与哺乳动物麻木蛋白直系同源物的相似度约为60%。有趣的是，znumb缺少Numbl直系同源物特有的两个特定序列基序。然而，znumb基因的染色体定位显示与位于小鼠和人类Numbl基因周围的基因具有共线性。此外，对麻木蛋白和Numbl蛋白中保守的磷酸酪氨酸结合（PTB）结构域序列进行的多物种比较表明，znumb与Numbl的关系比与麻木蛋白的关系更密切。znumb mRNA在多种斑马鱼成体组织中表达。在胚胎中过表达znumb会导致发育中的心脏管正常向左移位缺失或逆转。此外，在表达znumb的胚胎中未观察到或观察到双侧的lefty2转录本，这表明Notch信号对于斑马鱼左右场的形成和维持至关重要，并且znumb通过下调内源性Notch信号干扰了这一过程。
