The Atypical Cadherin Dachsous Controls Left-Right Asymmetry in Drosophila

• Myosin ID (MyoID) controls hindgut left-right (LR) asymmetry and dextral looping
• Drosophila atypical cadherin Dachsous (Ds) is essential for hindgut LR asymmetry
• MyoID interacts with Ds intracellular domain for proper LR asymmetry
• Ds propagates MyoID LR information from LR organizer to hindgut precursors

SummaryLeft-right (LR) asymmetry is essential for organ development and function in metazoans, but how initial LR cue is relayed to tissues still remains unclear. Here, we propose a mechanism by which the Drosophila LR determinant Myosin ID (MyoID) transfers LR information to neighboring cells through the planar cell polarity (PCP) atypical cadherin Dachsous (Ds). Molecular interaction between MyoID and Ds in a specific LR organizer controls dextral cell polarity of adjoining hindgut progenitors and is required for organ looping in adults. Loss of Ds blocks hindgut tissue polarization and looping, indicating that Ds is a crucial factor for both LR cue transmission and asymmetric morphogenesis. We further show that the Ds/Fat and Frizzled PCP pathways are required for the spreading of LR asymmetry throughout the hindgut progenitor tissue. These results identify a direct functional coupling between the LR determinant MyoID and PCP, essential for non-autonomous propagation of early LR asymmetry.

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