Expression profiling of mouse subplate reveals a dynamic gene network and disease association with autism and schizophrenia

Abstract

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.RNAseq | microarray | Nxph4 | Tpd52l1 | interstitial white matter cells

Common Genetic Variants and Risk of Brain Injury After Preterm Birth

“…This is consistent with recent data showing that preterm infants have higher rates of neuropsychiatric disease in adult life, 68 as well as the observation that schizophrenia-and autism-associated genes are overexpressed in developing mouse cortical subplate, 69 a region of specific vulnerability during preterm life. 70 Future research could focus on perturbations in neuronal migration and lipid metabolism in the causal pathway to preterm brain injury.…”

From sauropsids to mammals and back: New approaches to comparative cortical development

“…Subplate cells are some of the earliest generated neurons in cortex (Rakic and Kostovic, 1990; Hoerder‐Suabedissen et al, 2009; Oeschger et al, 2012; Hoerder‐Suabedissen, 2013). These studies strengthen the hypothesis that an embryonic subplate was present in the ancestors of mammals and that additional cellular populations evolved as cortical development and connectivity became more complex (Montiel et al, 2011; Wang et al, 2011a).…”

Extracortical origin of some murine subplate cell populations

“…At both E18 and P8, some RMTW-derived cells expressed complexin 3 (Cplx3; Figs. S1F and S2A), a synaptic protein and marker of early-born subplate neurons in the mouse (17).…”

“…The subplate is a heterogeneous cell population (6,17,32,33), with the wide variety of cell types suggesting multiple origins (34). Indeed, we have shown that different subplate cell populations are generated in both cortical and extracortical areas.…”