CDH10/CDH9, Synaptic pathway genes, and ASD
Pathway based association analysis suggest that specific genetic variants in this gene class may be involved in shaping the physical structure and functional connectivity of the brain, that leads to the clinical manifestation of ASD.Cell–cell adhesion is essential for multicellular organisms. Cadherins are calcium dependent intercellular glycoproteins. Based on their molecular structure, cadherins can be grouped into classic cadherins (type I and type II), demosomal cadherins, protocadherins, and other types of cadherins.
CDH10 and CDH9 encode type II classical cadherins from the cadherin superfamily, which represent transmembrane proteins that mediate calcium-dependent cell–cell adhesion. The nervous system is derived from neural tube, which is formed during neurulation, where the surface of the ectoderm folds in at the dorsal midline. N-cadherin is expressed ubiquitously in the neuroepithelium. This suggests that cadherins play a role in the early neural tube formation. One study which sought to find common genetic variants to implicate in ASD found A marked pattern of enrichment for CDH10 in the frontal cortex (Fig. 2a)—a region known to be important in ASDs.1
Recent genetic studies have identified several neuronal cell-adhesion genes, including NRXN1 (neurexin 1)35,36, CNTNAP2 CACNA1C (L type voltage-gated calcium channel), CNTNAP2, GRIK2 (glutamate receptor, ionotropic, kainate 2), NRXN1 and NLGN4X, also show suggestive evidence of association. These sources of evidence indicate a potential role for cell-adhesion molecules in the pathogenesis of ASDs. Besides the potential roles of the nearby CDH10 and CDH9 genes, pathway-based association analysis lend further support to neuronal cell-adhesion molecules in conferring susceptibility to ASDs, suggesting that specific genetic variants in this gene class may be involved in shaping the physical structure and functional connectivity of the brain, that leads to the clinical manifestations of ASDs.1
Cadherins and Schizophrenia
Autism was diagnosed as early childhood schizophrenia initially. Recently, it has suggested that mutations in the cadherin pathway may represent the link between the two disorders. CDH12 and CDH18 defects are linked to Schizophrenia.2
Catenin and Cadherin Pathway
Catenin and Cadherin Pathway The catenin and cadherin pathway is important for the cell adhesion. The Beta Catenin binds tightly to the cytoplasmic domain of type I Cadherins and plays a essential role in the structural organization and function of cadherin by linking cadherin through alpha-catenin to the actin cytoskeleton. Wnt are powerful regulators of cell proliferation and differentiation and their signalling pathway involves proteins that directly participate in both gene transcription and cell adhesion.
1. Wang et. al. Common genetic variants on 5p14.1 associate with autism spectrum disorders. Nature. 2009 May 28;459(7246):528-33. PMID 19404256
2. Singh SM et. al. Autism meets schizophrenia via cadherin pathway.Schizophr Res. 2010 Feb;116(2-3):293-4. PMID 19861233