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

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

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Actin Cytoskeleton / metabolism
  • Adaptor Proteins, Signal Transducing / genetics
  • Adaptor Proteins, Signal Transducing / metabolism*
  • Animals
  • Body Patterning*
  • Drosophila
  • Drosophila Proteins / genetics
  • Drosophila Proteins / metabolism*
  • Myosins / genetics
  • Myosins / metabolism

Substances

  • Adaptor Proteins, Signal Transducing
  • DAAM protein, Drosophila
  • Drosophila Proteins
  • Myosins

Grants and funding

This study was funded by PhD fellowships to A.C. ((ANR-11-LABX-0028-01), LABEX SIGNALIFE, Agence Nationale pour la Recherche, https://anr.fr/; Fondation pour la Recherche Médicale (FRM), https://www.frm.org/) and Postdoctoral fellowship to I.F. (Hungarian scientific research fund fellowship (OTKA)(PD128357)). Work in the J.M. laboratory is supported by Hungarian scientific research fund (OTKA)(K132782). Work in the S.N. laboratory is supported by Agence Nationale pour la Recherche (https://anr.fr/)(ANR-13-BSV2- 0006; ANR-17-CE13-0024), LABEX SIGNALIFE, http://signalife.unice.fr/), Initiatives d’Excellences, (IDEX UCAjedi)(https://anr.fr/ProjetIA-15-IDEX-0001#), Fondation pour la Recherche Médicale (FRM; https://www.frm.org/), Université Côte d’Azur (UCA; http://univ-cotedazur.fr/fr), Centre National pour la Recherche Scientifique (CNRS; www.cnrs.fr) and Institut National pour la Recherche Médicale (Inserm; https://www.inserm.fr/). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.