Jeb signals through the Alk receptor tyrosine kinase to drive visceral muscle fusion
Jeb signals through the Alk receptor tyrosine kinase to drive visceral muscle fusion
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DOI：
10.1038/nature01950
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发表时间：
2003-10-02
期刊：
影响因子：
64.8
通讯作者：
Palmer, RH
中科院分区：
文献类型：
--
作者：
Englund, C;Lorén, CE;Palmer, RH
果蝇基因间变性淋巴瘤激酶（Alk）与哺乳动物Alk同源，是受体酪氨酸激酶（RTK）的Alk/Ltk家族成员（1）。我们之前已经表明，果蝇Alk RTK在早期胚胎发生期间对内脏中胚层发育至关重要（2）。值得注意的是，观察到的Alk内脏中胚层缺陷高度地使人联想到分泌分子Jelly belly（Jeb）的表型（3）。在这里，我们表明果蝇Alk是发育中的内脏中胚层中Jeb的受体，并且Jeb结合刺激Alk驱动的细胞外信号调节激酶介导的信号传导途径，这导致下游基因duf（也称为kirre）的表达（4，5）-肌肉融合所需。这种新的信号转导途径驱动肌肉创始人细胞的规范，并通过果蝇Alk RTK调节Duf表达解释了在Alk和jeb突变动物中观察到的内脏-中胚层特异性肌肉融合缺陷。
The Drosophila melanogaster gene Anaplastic lymphoma kinase (Alk) is homologous to mammalian Alk, a member of the Alk/Ltk family of receptor tyrosine kinases (RTKs)(1). We have previously shown that the Drosophila Alk RTK is crucial for visceral mesoderm development during early embryogenesis(2). Notably, observed Alk visceral mesoderm defects are highly reminiscent of the phenotype reported for the secreted molecule Jelly belly (Jeb)(3). Here we show that Drosophila Alk is the receptor for Jeb in the developing visceral mesoderm, and that Jeb binding stimulates an Alk-driven, extracellular signal-regulated kinase-mediated signalling pathway, which results in the expression of the downstream gene duf (also known as kirre)(4,5)-needed for muscle fusion. This new signal transduction pathway drives specification of the muscle founder cells, and the regulation of Duf expression by the Drosophila Alk RTK explains the visceral-mesoderm-specific muscle fusion defects observed in both Alk and jeb mutant animals.