Englund Camilla, Lorén Christina E, Grabbe Caroline, Varshney Gaurav K, Deleuil Fabienne, Hallberg Bengt, Palmer Ruth H
Umeå Center for Molecular Pathogenesis, Umeå University, Umeå, S-901 87, Sweden.
Nature. 2003 Oct 2;425(6957):512-6. doi: 10.1038/nature01950.
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). We have previously shown that the Drosophila Alk RTK is crucial for visceral mesoderm development during early embryogenesis. Notably, observed Alk visceral mesoderm defects are highly reminiscent of the phenotype reported for the secreted molecule Jelly belly (Jeb). 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)--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.
果蝇黑腹果蝇基因间变性淋巴瘤激酶（Alk）与哺乳动物Alk同源，Alk是受体酪氨酸激酶（RTK）的Alk/Ltk家族成员。我们之前已经表明，果蝇Alk RTK在胚胎早期发育过程中对内脏中胚层的发育至关重要。值得注意的是，观察到的Alk内脏中胚层缺陷与报道的分泌分子果冻肚（Jeb）的表型高度相似。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结合刺激了由Alk驱动的、细胞外信号调节激酶介导的信号通路，这导致了下游基因duf（也称为kirre）的表达——这是肌肉融合所必需的。这条新的信号转导通路驱动肌肉始祖细胞的特化，并且果蝇Alk RTK对Duf表达的调节解释了在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。
