Expression profiling of mouse subplate reveals a dynamic gene network and disease association with autism and schizophrenia
Expression profiling of mouse subplate reveals a dynamic gene network and disease association with autism and schizophrenia
The subplate zone is a highly dynamic transient sector of the developing cerebral cortex that contains some of the earliest generated neurons and the first functional synapses of the cerebral cortex. Subplate cells have important functions in early establishment and maturation of thalamocortical connections, as well as in the development of inhibitory cortical circuits in sensory areas. So far no role has been identified for cells in the subplate in the mature brain and disease association of the subplate-specific genes has not been analyzed systematically. Here we present gene expression evidence for distinct roles of the mouse subplate across development as well as unique molecular markers to extend the repertoire of subplate labels. Performing systematic comparisons between different ages (embryonic days 15 and 18, postnatal day 8, and adult), we reveal the dynamic and constant features of the markers labeling subplate cells during embryonic and early postnatal development and in the adult. This can be visualized using the online database of subplate gene expression at https://molnar.dpag.ox.ac.uk/subplate/ . We also identify embryonic similarities in gene expression between the ventricular zones, intermediate zone, and subplate, and distinct postnatal similarities between subplate, layer 5, and layers 2/3. The genes expressed in a subplate-specific manner at some point during development show a statistically significant enrichment for association with autism spectrum disorders and schizophrenia. Our report emphasizes the importance of the study of transient features of the developing brain to better understand neurodevelopmental disorders.
- Imperial College London United Kingdom
- University of Oxford United Kingdom
- King's College Hospital NHS Foundation Trust United Kingdom
- MRC London Institute of Medical Sciences United Kingdom
- King's College London United Kingdom
SOMATOSENSORY CORTEX, Time Factors, SPECTRUM DISORDERS, THALAMOCORTICAL CONNECTIONS, Mice, interstitial white matter cells, CEREBRAL-CORTEX, 616, Tpd52l1, Nxph4, Animals, Gene Regulatory Networks, Genetic Predisposition to Disease, Protein Interaction Maps, BRAIN, Autistic Disorder, NEURONS, Genetic Association Studies, Cerebral Cortex, DEVELOPMENTAL HISTORY, Gene Expression Profiling, CORTICAL SUBPLATE, Gene Expression Regulation, Developmental, RNAseq, Mice, Inbred C57BL, DIFFERENTIATION, Animals, Newborn, Organ Specificity, Schizophrenia, WHITE-MATTER, microarray
SOMATOSENSORY CORTEX, Time Factors, SPECTRUM DISORDERS, THALAMOCORTICAL CONNECTIONS, Mice, interstitial white matter cells, CEREBRAL-CORTEX, 616, Tpd52l1, Nxph4, Animals, Gene Regulatory Networks, Genetic Predisposition to Disease, Protein Interaction Maps, BRAIN, Autistic Disorder, NEURONS, Genetic Association Studies, Cerebral Cortex, DEVELOPMENTAL HISTORY, Gene Expression Profiling, CORTICAL SUBPLATE, Gene Expression Regulation, Developmental, RNAseq, Mice, Inbred C57BL, DIFFERENTIATION, Animals, Newborn, Organ Specificity, Schizophrenia, WHITE-MATTER, microarray
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