Invertebrate insights into autism.

characterized by deficits in social communication and interaction, impaired language development, and stereotyped repetitive behaviors. The broader category of autism spectrum disorders (ASDs) includes individuals with subsets of these symptoms (Geschwind and Levitt, 2007). The prevalence of autism in the USA has increased since the inception of the diagnosis in the 1980s – to about 1 in every 110 children. The majority of this rise is attributed to greater screening efforts and expanded diagnostic criteria (Centers for Disease Control and Prevention, 2009). The study of autism is challenging because of the heterogeneous phenotypic presentation of the disease and the complexity of its inheritance, and no primary treatment exists. Although the genetic her-itability is high – with parental susceptibility genes contributing to an estimated 80% of cases – the polymorphic nature of autism has made identification of individual genes difficult (Freitag, 2007). Unraveling this genetic component is crucial to fully understanding ASDs. Investigations of familial autism have yielded several candidate genes, including neuroligin-3 and-4, which are associated with ASDs in a subset of family pedigrees (Jamain et al., 2003; Laumonnier et al., 2004; Yan et al., 2005). Neuroligins are post-synaptic cell adhesion molecules that bind to presynaptic neurexins and function in the maturation, stability and maintenance of synapses (Sudhof, 2008). This function of neuroligins is consistent with numerous lines of evidence supporting a role for neu-ronal connections, synaptogenesis and plasticity in autism (Levy et al., 2009). Discovering a role for neuroligins in autism had immediate implications for developing animal models of the disease. Most previously existing mouse models of autism represent co-morbid genetic disorders such as Rett syndrome or fragile X syndrome , with limited utility to address ASDs specifically. The mouse neuroligin-3-knockout model for autism generated excitement as the first monogenic animal model of autism (Radyushkin et al., 2009). A neu-roligin-1-knockout mouse soon followed (Blundell et al., 2010). Both sets of mice lack an obvious autistic phenotype, but display endophenotypes reminiscent of ASDs. Although complex animals such as mice have the best potential to recapitulate complex human behavioral phenotypes, organisms such as Caenorhabditis elegans, Drosophila melanogaster and Saccha-romyces cerevisiae provide powerful, tractable systems with which to elucidate the fundamental genetic and mechanistic causes of disease. In a recent issue of DMM, Hunter et al. report behavioral phenotypes consistent with ASDs following removal of the neu-roligin homolog, nlg-1, from C. elegans (Hunter et al., 2010). Through cDNA sequencing and reverse-transcriptase poly-merase …