title: The emerging roles of TCF4 in disease and development.
abstract: Genome-wide association studies have identified common variants in transcription factor 4 (TCF4) as susceptibility loci for schizophrenia, Fuchs' endothelial corneal dystrophy, and primary sclerosing cholangitis. By contrast, rare TCF4 mutations cause Pitt-Hopkins syndrome, a disorder characterized by intellectual disability and developmental delay, and have also been described in patients with other neurodevelopmental disorders. TCF4 therefore sits at the nexus between common and rare disorders. TCF4 interacts with other basic helix-loop-helix proteins, forming transcriptional networks that regulate the differentiation of several distinct cell types. Here, we review the role of TCF4 in these seemingly diverse disorders and discuss recent data implicating TCF4 as an important regulator of neurodevelopment and epithelial-mesenchymal transition.
authors.affiliation: Institute of Psychological Medicine and Clinical Neurosciences, MRC Centre for Neuropsychiatric Genetics and Genomics, School of Medicine, Cardiff University, Cardiff, UK.
authors.forename: Marc P
authors.initials: MP
authors.lastname: Forrest
authors.affiliation: Institute of Psychological Medicine and Clinical Neurosciences, MRC Centre for Neuropsychiatric Genetics and Genomics, School of Medicine, Cardiff University, Cardiff, UK.
authors.forename: Matthew J
authors.initials: MJ
authors.lastname: Hill
authors.affiliation: Structural Biophysics Group, School of Optometry and Vision Sciences, Cardiff University, Cardiff, UK.
authors.forename: Andrew J
authors.initials: AJ
authors.lastname: Quantock
authors.affiliation: Nuffield Division of Clinical Laboratory Sciences, Radcliffe Department of Medicine, University of Oxford, Oxford, UK; Stem Cell Research Laboratory, NHS Blood and Transplant, John Radcliffe Hospital, Oxford, UK.
authors.forename: Enca
authors.initials: E
authors.lastname: Martin-Rendon
authors.affiliation: Institute of Psychological Medicine and Clinical Neurosciences, MRC Centre for Neuropsychiatric Genetics and Genomics, School of Medicine, Cardiff University, Cardiff, UK. Electronic address: blakedj@cardiff.ac.uk.
authors.forename: Derek J
authors.initials: DJ
authors.lastname: Blake
mesh_terms: D051778:Basic Helix-Loop-Helix Leucine Zipper Transcription Factors / Q000235:genetics* / Q000378:metabolism; D051792:Basic Helix-Loop-Helix Proteins / Q000235:genetics; D003071:Cognition / Q000502:physiology; D058750:Epithelial-Mesenchymal Transition / Q000235:genetics; D019066:Facies; D005786:Gene Expression Regulation; D006801:Humans; D006985:Hyperventilation / Q000235:genetics*; D008607:Intellectual Disability / Q000235:genetics*; D057129:Iridocorneal Endothelial Syndrome / Q000235:genetics*; D008107:Liver Diseases / Q000235:genetics; D009154:Mutation; D012559:Schizophrenia / Q000235:genetics*; D000073940:Transcription Factor 4; D014157:Transcription Factors / Q000235:genetics* / Q000378:metabolism
chemical_list: D051778:Basic Helix-Loop-Helix Leucine Zipper Transcription Factors; D051792:Basic Helix-Loop-Helix Proteins; D000073940:Transcription Factor 4; D014157:Transcription Factors; C532096:TCF4 protein, human
keywords: Fuchs’ endothelial corneal dystrophy; Pitt–Hopkins syndrome; epithelial–mesenchymal transition; intellectual disability; schizophrenia; transcription