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

Anil Chougule,István Földi,Delphine Cerezo,Stéphane Noselli,François Lapraz,József Mihály,Hiroshi Hamada

doi:10.1371/journal.pgen.1008758

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.

Highlights

Left-Right (LR) asymmetry, or chirality, is a universal feature of living organisms
Aberrant LR asymmetry in human results in severe anatomical defects leading to embryonic lethality, spontaneous abortion and a number of congenital disorders
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

Summary

Introduction

Left-Right (LR) asymmetry, or chirality, is a universal feature of living organisms. It is essential to organs for their positioning (e.g., heart on the left side), lateralized differentiation (e.g., heart, lungs) and proper directional coiling (e.g., gut, heart tube). The study of LR asymmetry in model organisms has led to the identification of key molecular pathways and symmetry breaking mechanisms [1,2,3]. While vertebrates use directional movement of cells (chick), ions (Xenopus) or cilia-dependent nodal flow (mouse) as symmetry breaking processes, invertebrates (snail, nematode, Drosophila) establish LR asymmetry mostly through acto-myosinbased mechanisms. Work in Drosophila identified the conserved myosin1D (myo1D) gene as a major dextral determinant [4,5]. Several organs are chiral and undergo stereotyped looping in the dextral direction (testis, genitalia, gut)[11,12]. Loss of myo1D function leads to a sinistral or situs inversus phenotype, making organs undergo looping in the opposite direction. The genetic basis of sinistral asymmetry remains uncharacterized in any system, due to the lack of dedicated genetic screens to identify genes with a specific role in sinistral development

Methods

Results

Discussion

Conclusion