1. Developmental role of the cell adhesion molecule Contactin-6 in the cerebral cortex and hippocampus
- Author
-
Asami Oguro-Ando, van Dijk R, Amila Zuko, van der Zwaag B, J.P.H. Burbach, and Gregorio-Jordan S
- Subjects
0301 basic medicine ,Aging ,Cell Adhesion Molecules, Neuronal ,Hippocampus ,Cell Count ,03 medical and health sciences ,Cellular and Molecular Neuroscience ,0302 clinical medicine ,Interneurons ,Cortex (anatomy) ,medicine ,Animals ,Neuropeptide Y ,RNA, Messenger ,Cell adhesion ,Visual Cortex ,Cerebral Cortex ,biology ,Cell adhesion molecule ,Chemistry ,Pyramidal Cells ,Cell Biology ,Anatomy ,Cell biology ,Mice, Inbred C57BL ,Parvalbumins ,030104 developmental biology ,Visual cortex ,medicine.anatomical_structure ,Cerebral cortex ,Mossy Fibers, Hippocampal ,biology.protein ,Neural cell adhesion molecule ,030217 neurology & neurosurgery ,Parvalbumin ,Research Paper - 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.
- Published
- 2016