wnt5 interacts with the ryk receptors doughnut and derailed to mediate muscle attachment site selection in drosophila melanogasterwnt5与ryk受体交互甜甜圈和出轨调解肌肉附件选址在黑腹果蝇.pdf

WNT5 Interacts with the Ryk Receptors Doughnut and Derailed to Mediate Muscle Attachment Site Selection in Drosophila melanogaster Liza L. Lahaye, Rene R. Wouda, Anja W. M. de Jong, Lee G. Fradkin*, Jasprina N. Noordermeer* Laboratory of Developmental Neurobiology, Department of Molecular and Cell Biology, Leiden University Medical Center, Leiden, The Netherlands Abstract In recent years a number of the genes that regulate muscle formation and maintenance in higher organisms have been identified. Studies employing invertebrate and vertebrate model organisms have revealed that many of the genes required for early mesoderm specification are highly conserved throughout evolution. Less is known about the molecules that mediate the steps subsequent to myogenesis, e. g. myotube guidance and attachment to tendon cells. We use the stereotypic pattern of the Drosophila embryonic body wall musculature in genetic approaches to identify novel factors required for muscle attachment site selection. Here, we show that Wnt5 is needed in this process. The lateral transverse muscles frequently overshoot their target attachment sites and stably attach at novel epidermal sites in Wnt5 mutant embryos. Restoration of WNT5 expression in either the muscle or the tendon cell rescues the mutant phenotype. Surprisingly, the novel attachment sites in Wnt5 mutants frequently do not express the Stripe (SR) protein which has been shown to be required for terminal tendon cell differentiation. A muscle bypass phenotype was previously reported for embryos lacking the WNT5 receptor Derailed (DRL). drl and Wnt5 mutant embryos also exhibit axon path finding errors. DRL belongs to the conserved Ryk receptor tyrosine kinase family which includes two other Drosophila orthologs, the Doughnut on 2 (DNT)