PLoS Genet. 2020 Apr 23;16(4):e1008758. doi: 10.1371/journal.pgen.1008758. eCollection 2020 Apr.

Anil Chougule¹ , François Lapraz¹ , István Földi² , Delphine Cerezo¹ , József Mihály² , Stéphane Noselli¹

Affiliations

¹Université Côte D’Azur, CNRS, Inserm, iBV, Nice, France.
²Biological Research Centre, Hungarian Academy of Sciences, Institute of Genetics, Hungary.

Abstract

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.

PMID: 32324733
DOI: 10.1371/journal.pgen.1008758