The zebrafish nodal-related gene southpaw is required for visceral and diencephalic left-right asymmetry
The zebrafish nodal-related gene southpaw is required for visceral and diencephalic left-right asymmetry
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DOI：
10.1242/dev.00436
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发表时间：
2003-06-01
期刊：
影响因子：
4.6
通讯作者：
Rebagliati, M
中科院分区：
文献类型：
--
作者：
Long, S;Ahmad, N;Rebagliati, M
我们已经确定并描述了一种新的斑马鱼基因，左撇子，这是内脏和间脑左右不对称所必需的。Southpaw编码了淋巴结相关蛋白类的一个新成员，这是分泌因子转化生长因子β超家族中的一个亚家族。Southpaw在近轴中胚层前体中双侧表达，然后在左外侧板中胚层中表达。在某些发育后期，左撇子基因的表达会短暂地与其他标志心脏发育的基因（如lefty2）的左侧表达域重叠。我们已经注射了morpholinos来阻断southpaw mRNA的翻译或阻断southpaw pre-mRNA的剪接。这些morpholinos导致心脏左右不对称的早期（心脏慢跑）和晚期（心脏循环）方面的严重破坏。由于胰腺的左右不对称也受到影响，2303左撇子似乎调节了胚胎大部分的左右不对称。与形态变化一致，下游基因cyclops、pitx2、lefty1和lefty2的左侧表达域严重下调。或在缺乏南爪的胚胎的侧板中胚层内消失。令人惊讶的是，尽管大脑中没有左撇子的表达，但我们发现早期间脑左右不对称也需要左撇子的活动。这些观察结果导致了内脏器官和大脑左右不对称在胚胎发生过程中如何协调的模型。
We have identified and characterized a new zebrafish gene, southpaw, that is required for visceral and diencephalic left-right asymmetry. southpaw encodes a new member of the nodal-related class of proteins, a subfamily within the transforming growth factor beta superfamily of secreted factors. southpaw is expressed bilaterally in paraxial mesoderm precursors and then within the left lateral plate mesoderm. At late somite stages, left-sided southpaw expression transiently overlaps the left-sided expression domains of other genes that mark the developing heart, such as lefty2. We have injected morpholinos to block the translation of the southpaw mRNA or to block splicing of the southpaw pre-mRNA. These morpholinos cause a severe disruption of early (cardiac jogging) and late (cardiac looping) aspects of cardiac left-right asymmetry. As the left-right asymmetry of the pancreas is also affected, 2303 southpaw appears to regulate left-right asymmetry throughout a large part of the embryo. Consistent with the morphological changes, the left-sided expression domains of downstream genes (cyclops, pitx2, lefty1 and lefty2) are severely downregulated. or abolished within the lateral plate mesoderm of Southpaw-deficient embryos. Surprisingly, despite the absence of southpaw expression in the brain, we find that early diencephalic left-right asymmetry also requires Southpaw activity. These observations lead to a model of how visceral organ and brain left-right asymmetry are coordinated during embryogenesis.