L-R

The mechanisms underlying the establishment of left-right (L-R) asymmetry in bilaterians is one of the central enigmas in developmental biology. Amphioxus is an important model in studying the mechanisms of animal asymmetry specification due to its particular phylogenetic position, vertebrate-like embryogenesis and body plan. Recently, with the establishments of artificial breeding technology, high-efficiency microinjection method and gene knockout technology, researchers have successfully dissected the mechanisms of amphioxus L-R asymmetry development. In this review, we summarize the major progress in understanding L-R asymmetry specification in amphioxus and propose a model of regulation of L-R asymmetry in this species. Hh protein is transported dominantly to the right side by cilia movement, leading to R>L Hh signaling andCerexpression. Cer inhibits expression of Nodal, leading to the asymmetric expression of Nodal-dependent genes. The L-R differences in the propagation of the Nodal pathway result in the correct morphological L-R asymmetry development in amphioxus embryo. BMP signaling probably does not provide the asymmetric cue, but is necessary for correct expression ofCer andNodal.

Differentiating left and right hand sides during embryogenesis represents a major event in body patterning. Left-Right (L/R) asymmetry in bilateria is essential for handed positioning, morphogenesis and ultimately the function of organs (including the brain), with defective L/R asymmetry leading to severe pathologies in human. How and when symmetry is initially broken during embryogenesis remains debated and is a major focus in the field. Work done over the past 20 years, in both vertebrate and invertebrate models, has revealed a number of distinct pathways and mechanisms important for establishing L/R asymmetry and for spreading it to tissues and organs. In this review, we summarize our current knowledge and discuss the diversity of L/R patterning from cells to organs during evolution.

Vertebrates display left-right (L-R) asymmetric organ positioning and morphologies, which are established during embryonic development. These asymmetries are conserved among individuals and species. How, when and where do embryos first break the symmetry? Why is it broken in a consistent direction? How is the asymmetry transmitted to and coordinated within the whole embryo? Which of these elements are conserved between different organisms? These questions have been the focus of intense research during the last decade, and much has been learned. Nonetheless, our understanding of how tissue and organ L-R differences are established during embryogenesis is scarce. A systems biology approach may enable us to better understand the dynamics of gene networks, epigenetics, cilia, fluids, and charged molecules as well as other processes involved in the generation of the vertebrate L-R axis.