The Drosophila actin nucleator DAAM is essential for left-right asymmetry

Chougule, Anil and Lapraz, Francois and Földi, István and Cerezo, Delphine and Mihály, József (2020) The Drosophila actin nucleator DAAM is essential for left-right asymmetry. PLOS GENETICS, 16 (4). ISSN 1553-7390

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Abstract

Author summary Although our body looks symmetrical when viewed from the outside, it is in fact highly asymmetrical when we consider the shape and implantation of organs. For example, our heart is on the left side of the thorax, while the liver is on the right. In addition, our heart is made up of two distinct parts, the right heart and the left heart, which play different roles for blood circulation. These asymmetries, called left-right asymmetries, play a fundamental role in the morphogenesis and function of visceral organs and the brain. Aberrant LR asymmetry in human results in severe anatomical defects leading to embryonic lethality, spontaneous abortion and a number of congenital disorders. Our recent work has identified a particular myosin (Myo1D) as a major player in asymmetry in Drosophila and vertebrates. Myosins are proteins that can interact with the skeleton of cells (called the cytoskeleton) to transport other proteins, contract the cells, allow them to move, etc. In this work, we were able to identify all the genes of the cytoskeleton involved with myosin in left-right asymmetry, in particular a so-called 'nucleator' gene because it is capable of forming new parts of the cytoskeleton necessary for setting up asymmetries. Left-Right (LR) asymmetry is essential for organ positioning, shape and function. Myosin 1D (Myo1D) has emerged as an evolutionary conserved chirality determinant in both Drosophila and vertebrates. However, the molecular interplay between Myo1D and the actin cytoskeleton underlying symmetry breaking remains poorly understood. To address this question, we performed a dual genetic screen to identify new cytoskeletal factors involved in LR asymmetry. We identified the conserved actin nucleator DAAM as an essential factor required for both dextral and sinistral development. In the absence of DAAM, organs lose their LR asymmetry, while its overexpression enhances Myo1D-induced de novo LR asymmetry. These results show that DAAM is a limiting, LR-specific actin nucleator connecting up Myo1D with a dedicated F-actin network important for symmetry breaking.

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