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Jeb signals through the Alk receptor tyrosine kinase to drive visceral muscle fusion


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 embryogenesis2. 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.

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Figure 1: Jeb and Alk mutants show identical visceral mesoderm phenotypes.
Figure 2: Jeb and Alk are both required for activation of ERK and expression of Duf in muscle founder cells.
Figure 3: Jeb is taken up by Alk in the visceral mesoderm.
Figure 4: Alk kinase activity is required for the uptake of Jeb in the visceral mesoderm.


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The authors would like to thank T. Hunter and I. Salecker for critical reading of the manuscript, and D. Eriksson, N. Norgren and A. Sheikholvaezin for help with ELISA analysis. This work is funded by the Swedish Research Council and is also supported by The Swedish Society for Medical Research (SSMF), Åke Wibergs Fund, the Royal Swedish Academy of Sciences, Lars Hiertas Minne Fund, and the Cancer Research Fund of Northern Sweden. F.D. was supported by a post-doctoral fellowship from the Wenner-Grenska Foundation.

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Correspondence to Ruth H. Palmer.

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Englund, C., Lorén, C., Grabbe, C. et al. Jeb signals through the Alk receptor tyrosine kinase to drive visceral muscle fusion. Nature 425, 512–516 (2003).

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