5B). and AWC right (AWCR). Asymmetricdie-1expression is usually controlled in a fundamentally distinct manner in these two neuron pairs. Importantly, asymmetricdie-1expression controls the directionally asymmetric expression of gustatory receptor proteins in the ASE neurons and the antisymmetric expression of olfactory receptor proteins in the AWC neurons. These asymmetries serve to increase the ability of the animal to discriminate distinct chemosensory inputs. The body plan of most higher animals is largely bilaterally symmetric, yet there are deviations from bilaterality in visceral organ placement (Ludwig 1932) and nervous systems (Hobert et al. 2002;Rogers et al. 2013). Asymmetries come in two fundamentally distinct types. Antisymmetries refer to stochastic left/right asymmetries in which a specific feature is present on either the left or right side of an animal (Palmer 2005). For example, claw size in crustaceans and paw preference in many animals are antisymmetric. In contrast to antisymmetries, directional asymmetries refer to asymmetries that are stereotypically found on only one side of the animal (within at least 95% of animals in a populace) (Palmer 2005). For example, language production in the left hemisphere of the human brain is usually directional. Compared with developmental decisions along the anterior/posterior or dorsal/ventral axes, there are still fundamental gaps in our understanding of patterning along the left/right axis, particularly in the nervous system. Specifically, since UK-371804 the molecular and mechanistic basis of the establishment of asymmetries is generally poorly comprehended, it has not been possible to compare and perhaps find commonalities in the control of antisymmetries and directional asymmetries. Intriguingly, evolutionary tracing of left/right asymmetric features suggests that antisymmetries may be representative of an ancestral state that can become fixed FN1 to result in a directional asymmetry (Palmer 2004). However, the molecular basis for such an evolutionary progression UK-371804 is usually unclear. UK-371804 The nervous system of the nematodeCaenorhabditis elegansdisplays two striking examples of antisymmetry and directional asymmetry in distinct sensory systems. The AWC olfactory neuron pair expresses several G-protein-coupled receptor (GPCR)-type olfactory receptors in a stochastic, anti-correlated, left/right asymmetric manner (Fig. 1;Troemel et al. 1999;Bauer Huang et al. 2007). In contrast, the ASE gustatory neuron pair expresses putative chemoreceptors of the receptor-type guanylyl cyclase family (gcygenes) in a directionally asymmetric manner (Fig. 1;Yu et al. 1997;Ortiz et al. 2006). In both cases, asymmetric expression of chemoreceptors ensures that the left and right neurons are able to discriminate between distinct sensory cues (Pierce-Shimomura et al. 2001;Wes and Bargmann 2001;Ortiz et al. 2009). Such discrimination would not be possible if receptors were coexpressed in both left and right neurons. == Physique 1. == AWC and ASE asymmetry. Previously known components of genetic pathways that control UK-371804 AWC and ASE asymmetries. Not all genes known to be involved are shown. Black and gray gene names indicate whether a gene is usually more active or more expressed (black) in one neuron compared with the other neuron. Genetic screens for mutants that affect left/right asymmetric expression of the putative olfactory receptorstr-2in AWC left/right (AWCL/R) have revealed a transient neural network formed via NSY-5 gap junctions between distinct sensory neurons, including AWC (Chuang et al. 2007). A calcium-triggered signaling pathway operating downstream from this gap junction network establishes AWC asymmetry (Fig. 1;Sagasti et al. 2001;Chuang and Bargmann 2005). However, none of these mechanisms operate in the establishment of ASE asymmetry (Chang et al. 2003). Left/right asymmetry of the two ASE neurons is rather conferred by a Notch-dependent signaling event in the early embryo that establishes a specific chromatin UK-371804 state at a microRNA (miRNA) locus,lsy-6, in the precursors of the left ASE neuron (Poole and Hobert 2006;Cochella and Hobert 2012). After birth of the ASE left (ASEL) neuron, this miRNA then operates through a complex gene regulatory network to determine left/right asymmetricgcygene expression (Fig. 1;Hobert 2006). At the core of the gene regulatory network is the ASEL-restricted C2H2 zinc finger transcription factor DIE-1, whose loss results in a conversion of ASEL identity to ASE right.