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REVIEW Open AccessWnt signaling networks in autism spectrumdisorder and intellectual disabilityVickie Kwan, Brianna K. Unda and Karun K. Singh *AbstractBackground: Genetic factors play a major role in the risk for neurodevelopmental disorders such as autismspectrum disorders (ASDs) and intellectual disability (ID). The underlying genetic factors have become betterunderstood in recent years due to advancements in next generation sequencing. These studies have uncovered avast number of genes that are impacted by different types of mutations (e.g., de novo, missense, truncation, copynumber variations).Abstract: Given the large volume of genetic data, analyzing each gene on its own is not a feasible approach andwill take years to complete, let alone attempt to use the information to develop novel therapeutics. To make senseof independent genomic data, one approach is to determine whether multiple risk genes function in commonsignaling pathways that identify signaling “hubs” where risk genes converge. This approach has led to multiplepathways being implicated, such as synaptic signaling, chromatin remodeling, alternative splicing, and proteintranslation, among many others. In this review, we analyze recent and historical evidence indicating that multiplerisk genes, including genes denoted as high-confidence and likely causal, are part of the Wingless (Wnt signaling)pathway. In the brain, Wnt signaling is an evolutionarily conserved pathway that plays an instrumental role indeveloping neural circuits and adult brain function.Conclusions: We will also review evidence that pharmacological therapies and genetic mouse models furtheridentify abnormal Wnt signaling, particularly at the synapse, as being disrupted in ASDs and contributing to diseasepathology.Keywords: Autism spectrum disorders, ASD, Synapse, Wnt signaling, GSK3, Neurodevelopment, Signaling, Plasticity,Mutations, Neurotransmission, Neurogenesis, Neuronal migrationBackgroundThe emerging genetic landscape of Wnt signaling in ASDsASDs and other psychiatric disorders may have heritabil-ity estimates greater than 90% [1], suggesting a stronggenetic component to disease. With this background inmind, there has been an enormous advancement of newgenetic technologies to discover risk-causing genes andloci. These developments paired with an increased abilityto process large data sets have led to many new riskgenes being discovered. The number of genes andchromosomal loci linked to ASDs is growing, making itdifficult to determine which one(s) to study. This has in-spired the field to determine if there are links betweenthe genes and whether they converge into signalingnetworks important for proper brain development.While the spectrum of ASDs is reflected by the multipleindividual risk genes and loci, there is some common de-nominator between affected individuals, which stronglysuggests that disruption of the core neurodevelopmentalsignaling pathways leads to disease symptoms. In this re-view, we will examine accumulating evidence for the in-volvement of Wnt signaling in developmental cognitivedisorders. This includes emerging genetic data fromlarge sequencing studies, clinically used medications,and mouse models. We will also present potential ave-nues for therapeutic approaches, and how Wnt signalingmay be modulated for treatment of patient symptoms byleveraging clinical trial data from other fields.* Correspondence: singhk2@mcmaster.caDepartment of Biochemistry and Biomedical Sciences, Stem Cell and CancerResearch Institute, McMaster University, Hamilton, Ontario L8S 4K1, Canada© The Author(s). 2016 Open Access This article is distributed under the terms of the Creative Commons Attribution 4.0International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, andreproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link tothe Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver(http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.Kwan et al. Journal of Neurodevelopmental Disorders (2016) 8:45 DOI 10.1186/s11689-016-9176-3