Higher organisms are intrinsically asymmetric, and this seems to be important. In humans, partial situs inversus, a medical condition where the body's organs are positioned in a mirror image of normal, is usually an embryonic lethal condition, whereas complete situs inversus often goes undiagnosed until doctors fail to find hearts or appendices in the right place. Simpler organisms may be good places to seek the developmental basis for the decisions that make for asymmetric adults, except that asymmetry may not be immediately obvious.

Richard Poole and Oliver Hobert describe an intriguing example of asymmetry in the simple nematode Caenorhabditis elegans, where every single cell, and its progenitors, is known from the groundbreaking work of Brenner and colleagues. Although the nervous system appears to be symmetrical, some of the neurones within it show functional asymmetry. In particular, there are a pair of gustatory neurones, ASEL (left) and ASER (right) that are morphologically symmetrical and which sense distinct water-soluble molecules. While the paper by Poole and Hobert doesn't address why these neurones are asymmetrical, it does explain how this asymmetry is set up, and it is proven to result from a decision taken in the very early embryo.

The authors wanted to differentiate between two theories: whether the asymmetry is established in the very early embryo, long before the ASEL/ASER pair differentiate, or whether it is a late event that involves communication between the ASEL and ASER neurones themselves. These ideas draw from two rival theories of how bilateral animals develop: either that embryos are intrinsically symmetrical, and that asymmetry is imposed on this symmetrical ground state, or conversely that embryos are intrinsically asymmetric, and that symmetry is an acquired complex trait. How can these theories be tested?

The authors drew on the detailed knowledge of embryonic development in the worm and laser-ablated either the precursor of ASEL or of ASER to establish whether communication between the two neurones was necessary to establish asymmetry. In these organisms, one of the two neurones was completely absent but the other developed normally. So communication between ASEL and ASER was not required for them to differentiate.

Another possibility is that there is some molecule present in a spatially asymmetric way that cells can sense and so `read' their identity. To test this, the authors looked at mutants of a G-protein alpha (gpa-16),which participates in very early asymmetry decisions in the embryo. In gpa-16 mutants, the intrinsic slight asymmetry of the 6-cell embryo was randomized, as were the ASEL/ASER fates in the developed worms. However,was the randomization of ASEL and ASER fates due to a very early decision at the 6-cell stage, or were the ASEL/ASER cells reading environmental cues much later on? The authors made use of a temperature-sensitive mutant of gp-16. Knocking out gp-16 with higher temperatures after the 6-cell stage only had no impact on ASEL/ASER fate, showing that a decision at the 6-cell stage must be critical.

Further experiments showed that even this early asymmetry depended on the very first cell division of the fertilised egg, in which the anterior/posterior axis is established. Interestingly, the authors implicated Notch as a key player in these early decisions: the Drosophila homologue is a rather famous developmental gene that codes for a membrane receptor that binds several proteins, and interactions between these proteins help cells to decide their cell fates relative to their neighbours. Notch-like genes are found in many organisms, so this led the authors to speculate that their model of intrinsically asymmetric lineages arising from the very earliest stages of the embryo might have a general validity beyond gestation in this simple worm.

Poole, R. J. and Hobert, O. (
). Early embryonic programming of neuronal left/right asymmetry in C. elegans.
Curr. Biol.