Jeb signals through the Alk receptor tyrosine kinase to drive visceral muscle fusion.
ABSTRACT 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.
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ABSTRACT: Recent studies in invertebrates have provided important mechanistic insights into several general aspects of muscle development. Two new genes have been identified that are involved in muscle fusion in Drosophila and a novel maternal component was shown to be responsible for myogenic determination in an ascidian. In addition, genetic analyses of nematode and Drosophila homologues of factors known to be myogenic regulators in other species yielded surprising findings about both the evolutionary conservation and divergence of these functions. Drosophila myogenesis has become a highly informative model for understanding the interplay between the signaling and transcriptional networks that underlie cell-fate specification during embryonic development.Current Opinion in Genetics & Development 09/2001; 11(4):431-9. · 7.47 Impact Factor
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ABSTRACT: Background The mammalian receptor protein tyrosine kinase (RTK), Anaplastic Lymphoma Kinase (ALK), was first described as the product of the t(2;5) chromosomal translocation found in non-Hodgkin's lymphoma. While the mechanism of ALK activation in non-Hodgkin's lymphoma has been examined, to date, no in vivo role for this orphan insulin receptor family RTK has been described. Results We describe here a novel Drosophila melanogaster RTK, DAlk, which we have mapped to band 53 on the right arm of the second chromosome. Full-length DAlk cDNA encodes a phosphoprotein of 200 kDa, which shares homology not only with mammalian ALK but also with the orphan RTK LTK. Analysis of both mammalian and Drosophila ALK reveals that the ALK family of RTKs contains a newly identified MAM domain within their extracellular domains. Like its mammalian counterpart, DAlk appears to be expressed in the developing CNS by in situ analysis. However, in addition to expression of DAlk in the Drosophila brain, careful analysis reveals an additional early role for DAlk in the developing visceral mesoderm where its expression is coincident with activated ERK. Conclusion In this paper we describe a Drosophila melanogaster Alk RTK which is expressed in the developing embryonic mesoderm and CNS. Our data provide evidence for the existence of a DAlk RTK pathway in Drosophila. We show that ERK participates in this pathway, and that it is activated by DAlk in vivo. Expression patterns of dALK, together with activated ERK, suggest that DAlk fulfils the criteria of the missing RTK pathway, leading to ERK activation in the developing visceral mesoderm.Genes to Cells 05/2001; 6(6):531 - 544. · 2.73 Impact Factor
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ABSTRACT: The visceral musculature of the Drosophila midgut consists of an inner layer of circular and an outer layer of longitudinal muscles. Here, we show that the circular muscles are organised as binucleate syncytia that persist through metamorphosis. At stage 11, prior to the onset of the fusion processes, we detected two classes of myoblasts within the visceral trunk mesoderm. One class expresses the founder-cell marker rP298-LacZ in a one- to two-cells-wide strip along the ventralmost part of the visceral mesoderm, whereas the adjacent two to three cell rows are characterised by the expression of Sticks-and-stones (SNS). During the process of cell fusion at stage 12 SNS expression decreases within the newly formed syncytia that spread out dorsally over the midgut. At both margins of the visceral band several cells remain unfused and continue to express SNS. Additional rP298-LacZ-expressing cells arise from the posterior tip of the mesoderm, migrate anteriorly and eventually fuse with the remaining SNS-expressing cells, generating the longitudinal muscles. Thus, although previous studies proposed a separate primordium for the longitudinal musculature located at the posteriormost part of the mesoderm anlage, our cell lineage analyses as well as our morphological observations reveal that a second population of cells originates from the trunk mesoderm. Mutations of genes that are involved in somatic myoblast fusion, such as sns, dumbfounded (duf) or myoblast city (mbc), also cause severe defects within the visceral musculature. The circular muscles are highly unorganised while the longitudinal muscles are almost absent. Thus the fusion process seems to be essential for a proper visceral myogenesis. Our results provide strong evidence that the founder-cell hypothesis also applies to visceral myogenesis, employing the same genetic components as are used in the somatic myoblast fusion processes.Mechanisms of Development 02/2002; 110(1-2):85-96. · 2.38 Impact Factor