title: Developmental role of the cell adhesion molecule Contactin-6 in the cerebral cortex and hippocampus.
abstract: The gene encoding the neural cell adhesion molecule Contactin-6 (Cntn6 a.k.a. NB-3) has been implicated as an autism risk gene, suggesting that its mutation is deleterious to brain development. Due to its GPI-anchor at Cntn6 may exert cell adhesion/receptor functions in complex with other membrane proteins, or serve as a ligand. We aimed to uncover novel phenotypes related to Cntn6 functions during development in the cerebral cortex of adult Cntn6(-/-) mice. We first determined Cntn6 protein and mRNA expression in the cortex, thalamic nuclei and the hippocampus at P14, which decreased specifically in the cortex at adult stages. Neuroanatomical analysis demonstrated a significant decrease of Cux1+ projection neurons in layers II-IV and an increase of FoxP2+ projection neurons in layer VI in the visual cortex of adult Cntn6(-/-) mice compared to wild-type controls. Furthermore, the number of parvalbumin+ (PV) interneurons was decreased in Cntn6(-/-) mice, while the amount of NPY+ interneurons remained unchanged. In the hippocampus the delineation and outgrowth of mossy fibers remained largely unchanged, except for the observation of a larger suprapyramidal bundle. The observed abnormalities in the cerebral cortex and hippocampus of Cntn6(-/-) mice suggests that Cntn6 serves developmental functions involving cell survival, migration and fasciculation. Furthermore, these data suggest that Cntn6 engages in both trans- and cis-interactions and may be involved in larger protein interaction networks.
authors.affiliation: a Brain Center Rudolf Magnus , Department of Translational Neuroscience , University Medical Center Utrecht , Utrecht , The Netherlands.
authors.forename: Amila
authors.initials: A
authors.lastname: Zuko
authors.affiliation: a Brain Center Rudolf Magnus , Department of Translational Neuroscience , University Medical Center Utrecht , Utrecht , The Netherlands.
authors.forename: Asami
authors.initials: A
authors.lastname: Oguro-Ando
authors.affiliation: a Brain Center Rudolf Magnus , Department of Translational Neuroscience , University Medical Center Utrecht , Utrecht , The Netherlands.
authors.forename: Roland
authors.initials: R
authors.lastname: van Dijk
authors.affiliation: a Brain Center Rudolf Magnus , Department of Translational Neuroscience , University Medical Center Utrecht , Utrecht , The Netherlands.
authors.forename: Sara
authors.initials: S
authors.lastname: Gregorio-Jordan
authors.affiliation: b Department of Genetics , University Medical Center Utrecht , Utrecht , The Netherlands.
authors.forename: Bert
authors.initials: B
authors.lastname: van der Zwaag
authors.affiliation: a Brain Center Rudolf Magnus , Department of Translational Neuroscience , University Medical Center Utrecht , Utrecht , The Netherlands.
authors.forename: J Peter H
authors.initials: JP
authors.lastname: Burbach
mesh_terms: D000375:Aging / Q000378:metabolism; D000818:Animals; D015816:Cell Adhesion Molecules, Neuronal / Q000235:genetics / Q000378:metabolism*; D002452:Cell Count; D002540:Cerebral Cortex / Q000254:growth & development* / Q000378:metabolism*; D006624:Hippocampus / Q000254:growth & development* / Q000378:metabolism*; D007395:Interneurons / Q000378:metabolism; D008810:Mice, Inbred C57BL; D019599:Mossy Fibers, Hippocampal / Q000378:metabolism; D009478:Neuropeptide Y / Q000378:metabolism; D010320:Parvalbumins / Q000378:metabolism; D017966:Pyramidal Cells / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D014793:Visual Cortex / Q000378:metabolism
chemical_list: D015816:Cell Adhesion Molecules, Neuronal; D009478:Neuropeptide Y; D010320:Parvalbumins; D012333:RNA, Messenger; C526283:contactin 6 protein, mouse
keywords: ASD; CAMs; Cntn6; NB-3; autism; cell adhesion molecule; contactin; hippocampus; visual cortex