The Fes/Fer non-receptor tyrosine kinase cooperates with Src42A to regulate dorsal closure in Drosophila
Michael J Murray1, Catherine M Davidson, Neil M Hayward
1The Gurdon Institute and Department of Physiology, Development and Neuroscience, University of Cambridge, Tennis Court Road, Cambridge CB2 1QN, UK.
Abstract:
Fes/Fer non-receptor tyrosine kinases regulate cell adhesion and cytoskeletal reorganisation through the modification of adherens junctions. Unregulated Fes/Fer kinase activity has been shown to lead to tumours in vivo. Here, we show that Drosophila Fer localises to adherens junctions in the dorsal epidermis and regulates a major morphological event, dorsal closure. Mutations in Src42A cause defects in dorsal closure similar to those seen in dfer mutant embryos. Furthermore, Src42A mutations enhance the dfer mutant phenotype, suggesting that Src42A and DFer act in the same cellular process. We show that DFer is required for the formation of the actin cable in leading edge cells and for normal rates of dorsal closure. We have isolated a gain-of-function mutation in dfer (dfergof) that expresses an N-terminally fused form of the protein, similar to oncogenic forms of vertebrate Fer. dfergof blocks dorsal closure and causes axon misrouting. We find that in dfer loss-of-function mutants beta-catenin is hypophosphorylated, whereas in dfergof beta-catenin is hyperphosphorylated. Phosphorylated beta-catenin is removed from adherens junctions and degraded, thus implicating DFer in the regulation of adherens junctions.
Insights
Drosophila Fer (DFer) kinase regulates cell adhesion and embryonic development. DFer and Src42A function together in dorsal closure, with DFer controlling beta-catenin phosphorylation at adherens junctions.
Area of Science:
- Cell Biology
- Developmental Biology
- Molecular Genetics
Background:
- Fes/Fer non-receptor tyrosine kinases are crucial for cell adhesion and cytoskeletal dynamics.
- Aberrant Fes/Fer kinase activity is linked to tumorigenesis.
- Adherens junctions are key structures regulated by these kinases.
Purpose of the Study:
- To investigate the role of Drosophila Fer (DFer) in embryonic development, specifically dorsal closure.
- To determine the relationship between DFer and Src42A in cellular processes.
- To elucidate the mechanism by which DFer regulates adherens junctions.
Main Methods:
- Analysis of Drosophila melanogaster mutants for dfer and Src42A.
- Observation of dorsal closure and axon guidance.
- Examination of beta-catenin phosphorylation and localization.
Main Results:
- DFer localizes to adherens junctions and is essential for dorsal closure.
- Src42A mutations phenocopy and enhance dfer mutations, indicating a shared pathway.
- DFer is required for actin cable formation and regulates beta-catenin phosphorylation status.
Conclusions:
- DFer and Src42A function in the same cellular pathway regulating dorsal closure.
- DFer plays a critical role in maintaining adherens junction integrity through beta-catenin regulation.
- Dysregulation of DFer, similar to oncogenic vertebrate Fer, disrupts embryonic development.
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