Left–Right Asymmetry: The embryo's one-sided genes

The origin of left-right asymmetry during vertebrate embryogenesis has long been a puzzle; now, for the first time, genes have been identified that are expressed with left-right asymmetric patterns in early embryos. Unlike some politicians, vertebrate embryos can tell their left from right. The body plan of vertebrates, although externally symmetrical about the midline, exhibits considerable asymmetry in the visceral organs. The heart provides the most striking example; it forms as a simple tube at the midline, but this loops to one side and ends up both functionally and morphologically very different in its left and right parts. In mammals, the two lungs similarly follow distinct morphological pathways to leave each with a different number of lobes. Most individual organs-stomach, spleen, pancreas and liver, for example-lie to one side of the midline. In normal development, this asymmetry is invariant, or handed, such that the heart tube always loops to the right, there are more lung lobes on the right, the stomach is on the left, and so on. How the information for this plan is specified has been a puzzle for over a century, but a recent paper by Levin et al. [1] has shed some light on the molecules that may be involved. This paper describes, for the first time, left-right asymmetries in gene expression, and shows how these may be part of a pathway specifying handed asymmetry. Levin et al. [1] selected genes that are known to play roles in the early development of vertebrates, and examined their expression in chick embryos, specifically looking for left-right differences in expression. They looked at the expression of Hox genes, goosecoid, Sonic hedgehog (Shh), nodal-related 1 (cNR-1, which encodes a member of the transforming growth factor 13 (TGF3) family of secreted signalling molecules), activin receptors (activins are also TGF3 family members), fibroblast growth factors (FGFs) and HNF33 (which encodes a transcription factor initially found in liver and related to the Drosophila forkhead gene product). While most were found to be symmetrically expressed, four were not: Shh, HNF3, cNR-1 and the activin type IIa receptor gene (cAct-RIla). The earliest observed asymmetry was at stage 4, when the primitive streak has formed at the midline, and Hensen's node appears at its anterior end (Fig. 1). cAct-RIla was initially expressed more strongly in the right side of the primitive streak, and from stage 4 onwards its expression was restricted exclusively to the right half …