title: Contactin-5 expression during development and wiring of the thalamocortical system.
abstract: The gene encoding the neural cell adhesion molecule Cntn5 (a.k.a. NB-2) has been put forward as a candidate in neurodevelopmental disorders, like autism spectrum disorder (ASD), by recent genetic findings. Little is known about the expression pattern and function of the gene, and its functional involvement in brain development has remained elusive. So far, most research has focused on its early postnatal expression in the auditory system, where the absence of Cntn5 causes abnormal responses to acoustic stimuli and a decrease in fiber density. The current study shows that the Cntn5 gene is expressed in forebrain structures during embryonic development, starting at E15.5, and that it continues to be expressed into adulthood. Sites of strong expression included the thalamus, the caudate putamen (CPu) and to a lesser extent layer Va of the cerebral cortex. Cntn5-positive thalamic nuclei include the laterodorsal (LD), ventrolateral (VL) and posterior group (Po), which contain glutamatergic neurons. Visualization of the expression pattern through the Tau-LacZ fusion protein coded by an insert in the Cntn5 gene, demonstrated that Cntn5-positive nuclei of the thalamus project to the cortex, based on co-localization with thalamocortical markers L1 and Calretinin. These results indicate that the cell adhesion functions of Cntn5 are exploited for circuit formation and connectivity in early development and for synaptic maintenance during adulthood. Subtle alterations in the formation of the thalamocortical circuit may contribute to neurodevelopmental disorders, such as ASD.
authors.affiliation: Department of Translational Neuroscience, Brain Center Rudolf Magnus, UMC Utrecht, Stratenum 4.205, P.O. Box 85060, 3508 AB Utrecht, The Netherlands.
authors.forename: K T E
authors.initials: KT
authors.lastname: Kleijer
authors.affiliation: Department of Translational Neuroscience, Brain Center Rudolf Magnus, UMC Utrecht, Stratenum 4.205, P.O. Box 85060, 3508 AB Utrecht, The Netherlands.
authors.forename: A
authors.initials: A
authors.lastname: Zuko
authors.affiliation: Department of Bioengineering, Nagaoka University of Technology, 1603-1, Kamitomiokamachi, Nagaoka, Niigata 940-2188, Japan.
authors.forename: Y
authors.initials: Y
authors.lastname: Shimoda
authors.affiliation: National Institute of Technology, Nagaoka College, Nagaoka, Niigata 940-8532, Japan.
authors.forename: K
authors.initials: K
authors.lastname: Watanabe
authors.affiliation: Department of Translational Neuroscience, Brain Center Rudolf Magnus, UMC Utrecht, Stratenum 4.205, P.O. Box 85060, 3508 AB Utrecht, The Netherlands. Electronic address: j.p.h.burbach@umcutrecht.nl.
authors.forename: J P H
authors.initials: JP
authors.lastname: Burbach
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism; D018797:Cell Cycle Proteins / Q000235:genetics / Q000378:metabolism; D002540:Cerebral Cortex / Q000196:embryology / Q000254:growth & development / Q000378:metabolism; D045424:Complex Mixtures / Q000378:metabolism; D058966:Contactins / Q000235:genetics / Q000378:metabolism*; D004622:Embryo, Mammalian; D018507:Gene Expression Regulation, Developmental / Q000235:genetics*; D051379:Mice; D008822:Mice, Transgenic; D009434:Neural Pathways / Q000502:physiology; D009474:Neurons / Q000378:metabolism*; D013788:Thalamus / Q000196:embryology / Q000254:growth & development / Q000378:metabolism; D014157:Transcription Factors / Q000378:metabolism; D050599:Vesicular Glutamate Transport Protein 2 / Q000378:metabolism; D001616:beta-Galactosidase / Q000235:genetics / Q000378:metabolism
chemical_list: D002352:Carrier Proteins; D018797:Cell Cycle Proteins; D045424:Complex Mixtures; D058966:Contactins; D014157:Transcription Factors; D050599:Vesicular Glutamate Transport Protein 2; D001616:beta-Galactosidase; C501070:RBBP8 protein, mouse; C493477:Slc17a6 protein, mouse; C051709:glutamevit
keywords: autism spectrum disorder; contactin-5; development; thalamocortical circuit; thalamus