An Innexin-Dependent Cell Network Establishes Left-Right Neuronal Asymmetry in C. elegans

Abstract

Gap junctions are widespread in immature neuronal circuits, but their functional significance is poorly understood. We show here that a transient network formed by the innexin gap-junction protein NSY-5 coordinates left-right asymmetry in the developing nervous system of Caenorhabditis elegans. nsy-5 is required for the left and right AWC olfactory neurons to establish stochastic, asymmetric patterns of gene expression during embryogenesis. nsy-5-dependent gap junctions in the embryo transiently connect the AWC cell bodies with those of numerous other neurons. Both AWCs and several other classes of nsy-5-expressing neurons participate in signaling that coordinates left-right AWC asymmetry. The right AWC can respond to nsy-5 directly, but the left AWC requires nsy-5 function in multiple cells of the network. NSY-5 forms hemichannels and intercellular gap-junction channels in Xenopus oocytes, consistent with a combination of cell-intrinsic and network functions. These results provide insight into gap-junction activity in developing circuits.

The Expression of Tubulin and Tektin Genes in Dicyemid Mesozoans (Phylum: Dicyemida)

“…Several, organ-specific innexin genes were reported in a leech, H. medicinalis (Dykes and Macagno, 2006), in Drosophila melanogaster (Drosophilidae) (Stebbings et al, 2002), and in C. elegans (Starich et al, 2003;Chuang et al, 2007;Whitten and Miller, 2007). In embryonic stages, they were exclusively expressed in germ layers, but the dicyemid innexin was expressed in all blastomeres of developing embryos after the 24-cell stage.…”

Far from solved: A perspective on what we know about early mechanisms of left–right asymmetry

“…1). The specifics (e.g., spatial distribution, timing) differ among model species with divergent early embryonic architectures, these and the other biophysical components elucidated in Xenopus have now also been shown to be required for asymmetry in sea urchin (Duboc et al, 2005;Hibino et al, 2006), Ciona (Shimeld and Levin, 2006), chick (Levin et al, 2002;Raya et al, 2004;Adams et al, 2006), zebrafish (Adams et al, 2006), C. elegans (Chuang et al, 2007), and snails (Shibazaki et al, 2004).…”

“…In frog, the bioelectrical LR gradient appears to redistribute serotonin, a small molecule morphogen, which subsequently induces asymmetric gene expression (Fukumoto et al, 2005a,b;Adams et al, 2006;Levin et al, 2006). The rapid redistribution of serotonin among blastomeres (Fukumoto et al, 2005b) leads to stable, specific gene expression cascades on the left side; a similar situation occurs in C. elegans, where the NSY-5 gap junction protein establishes transient connections for physiological signals that specify the permanent asymmetry in the structure and function of the AWC olfactory neurons (Chuang et al, 2007). Similarly, as very early cytoskeletal biases in Xenopus ultimately result in asymmetries of visceral organs , the transduction of chiral cytoskeletal activity into asymmetric Nodal induction has recently been demonstrated in snail embryos; alterations in spindle orientations by means of mechanical manipulations in early cleavage stage embryos alter the Nodal signaling pathway as well as handedness of shell coiling (Kuroda et al, 2009).…”

Transcriptional regulation and stabilization of left–right neuronal identity in C. elegans

“…The NSY-5 gap junction network observed in electron micrographs disappears after hatching, and the downstream signaling pathway apparently becomes inactive as well (Chuang and Bargmann 2005;Chuang et al 2007). AWC left-right asymmetry is stable throughout the lifetime of the animal, so these transient signaling events must be captured and stabilized by molecules that act after embryogenesis.…”

“…This element of randomness is unusual in C. elegans, which is otherwise notable for the predictability of its cell fate decisions (Sulston and Horvitz 1977). The initial AWC ON /AWC OFF decision depends on a signaling pathway in which a claudin-like transmembrane protein, NSY-4, and an embryonic gap junction network generated by the innexin NSY-5 induce one AWC to exit the AWC OFF default identity and become AWC ON (Vanhoven et al 2006;Chuang et al 2007). The induced AWC ON neuron then provides feedback to the contralateral neuron to stabilize the AWC OFF identity.…”