The subplate lays the foundation of the developing cerebral cortex, and abnormalities have been suggested to contribute to various brain developmental disorders. The causal relationship between cellular pathologies and cognitive disorders remains unclear, and therefore, a better understanding of the role of subplate cells in cortical development is essential. Only by determining the molecular taxonomy of this diverse class of neurons can we identify the subpopulations that may contribute differentially to cortical development. We identified novel markers for murine subplate cells by comparing gene expression of subplate and layer 6 of primary visual and somatosensory cortical areas of postnatal day (P)8 old mice using a microarray-based approach. We examined the utility of these markers in well-characterized mutants (reeler, scrambler, and p35-KO) where the subplate is displaced in relation to the cortical plate. In situ hybridization or immunohistochemistry confirmed subplate-selective expression of complexin 3, connective tissue growth factor, nuclear receptor-related 1/Nr4a2, and monooxygenase Dbh-like 1 while transmembrane protein 163 also had additional expression in layer 5, and DOPA decarboxylase was also present in the white matter. Localization of marker-positive cells in the reeler and p35-KO cortices suggests different subpopulations of subplate cells. These new markers open up possibilities for further identification of subplate subpopulations in research and in neuropathological diagnosis.

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

There is currently a debate about the evolutionary origin of the earliest generated cortical preplate neurons and their derivatives (subplate and marginal zone). We examined the subplate with murine markers including nuclear receptor related 1 (Nurr1), monooxygenase Dbh-like 1 (Moxd1), transmembrane protein 163 (Tmem163), and connective tissue growth factor (Ctgf) in developing and adult turtle, chick, opossum, mouse, and rat. Whereas some of these are expressed in dorsal pallium in all species studied (Nurr1, Ctgf, and Tmem163), we observed that the closely related mouse and rat differed in the expression patterns of several others (Dopa decarboxylase, Moxd1, and thyrotropin-releasing hormone). The expression of Ctgf, Moxd1, and Nurr1 in the oppossum suggests a more dispersed subplate population in this marsupial compared with mice and rats. In embryonic and adult chick brains, our selected subplate markers are primarily expressed in the hyperpallium and in the turtle in the main cell dense layer of the dorsal cortex. These observations suggest that some neurons that express these selected markers were present in the common ancestor of sauropsids and mammals.

Lead‐based perovskite light‐emitting diodes (PeLEDs) have exhibited excellent purity, high efficiency, and good brightness. In order to develop nontoxic, highly luminescent metal halide perovskite materials, tin, copper, germanium, zinc, bismuth, and other lead‐free perovskites have been developed. Here, a novel 0D manganese‐based (Mn‐based) organic–inorganic hybrid perovskite with the red emission located at 629 nm, high photoluminescence quantum yield of 80%, and millisecond level triplet lifetime is reported. When applied as the emissive layer in the PeLEDs, the maximum recording brightness of devices after optimization is 4700 cd m−2, and the peak external quantum efficiency is 9.8%. The half‐life of the device reaches 5.5 h at 5 V. The performance and stability of Mn‐based PeLEDs are one order of magnitude higher than those of other lead‐free PeLEDs. This work clearly shows that the Mn‐based perovskite will provide another route to fabricate stable and high‐performance lead‐free PeLEDs.

The thorniest problem in comparative neurobiology is the identification of the particular brain region of birds and reptiles that corresponds to the mammalian neocortex [Butler AB, Reiner A, Karten HJ (2011) Ann N Y Acad Sci 1225:14-27; Wang Y, BrzozowskaPrechtl A, Karten HJ (2010) Proc Natl Acad Sci USA 107(28):12676-12681]. We explored which genes are actively transcribed in the regions of controversial ancestry in a representative bird (chicken) and mammal (mouse) at adult stages. We conducted four analyses comparing the expression patterns of their 5,130 most highly expressed one-to-one orthologous genes that considered global patterns of expression specificity, strong gene markers, and coexpression networks. Our study demonstrates transcriptomic divergence, plausible convergence, and, in two exceptional cases, conservation between specialized avian and mammalian telencephalic regions. This large-scale study potentially resolves the complex relationship between developmental homology and functional characteristics on the molecular level and settles long-standing evolutionary debates.cerebral cortex | Wulst | equivalent circuit hypothesis | brain evolution | dorsal ventricular ridge D espite recent advances in our knowledge of comparative aspects of cortical neurogenesis, migration, clonal relationships, and gene expression patterns, there is no consensus on how these processes evolved together to determine the adult brain structures across diverse amniotes (1-5). Anatomical, hodological, embryological, and gene expression data (based on few select genes) provide conflicting answers on brain homology across vertebrates. Studies of embryonic neurogenesis and cell migration have informed homology of developmental territories (6-8), but the striking similarities in lamination, connectivity, and physiological properties observed between adult forms derived from noncorresponding pallial regions remain unexplained (3-5, 9). Comparative transcriptomics is a powerful approach to interrogating regional correspondence without resorting to limited lists of selected genetic markers. Recent methodological advances in profiling mammalian cerebral cortical layer transcriptomes (10-12) could objectively test the validity of proposed, yet controversial, relationships between regions of adult mammalian and avian brains. These comparisons are motivated by our understanding of the evolution of mammals from a reptilian subclass, represented by the synapsid condition (with a cranial opening in the cheek region of the skull), and of birds from another reptilian subclass, represented by the diapsid condition (two postorbital skull openings). ResultsWe extended our previous transcriptomic analysis of cortical layers in the adult mouse (13) to additional structures, 16 in total, and compared these with seven regions of the adult chicken brain (Fig. 1A and SI Appendix, Figs. S1 and S2). All dissected regions in both species (except the striatum, which is subpallial) develop primarily from one of four morphogenetically delineated sector...

We investigated the expression and role of the dopamine receptor 3 (D3R) in postnatal mouse subventricular zone (SVZ). In situ hybridization detected selective D3R mRNA expression in the SVZ. Fluorescence activated cell sorting (FACS) of adult SVZ subtypes using hGFAP-GFP and Dcx-GFP mice showed that transit amplifying progenitor cells and niche astrocytes expressed D3R whereas stem cell-like astrocytes and neuroblasts did not. To determine D3R's role in SVZ neurogenesis, we administered U-99194A, a D3R preferential antagonist, and bromodeoxyuridine in postnatal mice. In vivo D3R antagonism decreased the numbers of newborn neurons reaching the core and the periglomerular layer of the olfactory bulb. Moreover, it decreased progenitor cell proliferation but did not change the number of label-retaining (stem) cells, commensurate with its expression on transit amplifying progenitor cells but not SVZ stem cell-like astrocytes. Collectively, this study suggests that dopaminergic stimulation of D3R drives proliferation via rapidly amplifying progenitor cells to promote murine SVZ neurogenesis. Keywords: dopamine receptor 3, neurogenesis, proliferation, stem cells, subventricular zone, U-99194A. Ó 2010 The Authors dopamine receptors, D3R is the only one specifically expressed in neurogenic areas, both in the embryonic and postnatal rat SVZ (Diaz et al. 1997;Araki et al. 2007). Therefore in this study we focussed on understanding D3R's role in postnatal SVZ neurogenesis. The postnatal SVZ is composed of three major neurogenic cell types; slowly proliferating astrocyte-like stem cells, transit amplifying progenitor cells, and migratory neuroblasts (Alvarez-Buylla and Garcia-Verdugo 2002). As each SVZ subtype has different biological properties, it is essential to understand which specific dopamine receptors are expressed by which SVZ cell. However, the lack of reliable dopamine receptor antibodies has made it difficult to identify dopamine receptor expression in SVZ cells. To circumvent this issue, we used FACS to isolate SVZ subtypes based on marker expression and two different GFP+ reporter mice (Nam et al. 2007;Pastrana et al. 2009).The dopamine 3 receptor's role in regulating postnatal SVZ neurogenesis remains controversial. D3R stimulation in adult rats increased SVZ proliferation (Coronas et al. 2004;Van Kampen et al. 2004). However, similar treatments with D3R specific agonists failed to show any effect in adult mouse SVZ (Baker et al. 2005). Thus, there are several specific inconsistencies in the literature despite ample evidence that in general dopamine affects postnatal SVZ neurogenesis. Here, we investigated the role and mechanism of D3R in murine postnatal neurogenesis. We provide evidence that D3R is expressed in rapidly amplifying progenitor cells in the postnatal SVZ and drives cell proliferation to regulate olfactory bulb neurogenesis. Materials and methodsAnimals Doublecortin-GFP (Dcx-GFP) mice were originally developed by the Rockefeller GENSAT Project (Gong et al. 2003). hGFAP-GFP mice were obta...

The subplate is a largely transient zone containing precocious neurons involved in several key steps of cortical development. The majority of subplate neurons form a compact layer in mouse, but are dispersed throughout a much larger zone in the human. In rodent, subplate neurons are among the earliest born neocortical cells, whereas in primate, neurons are added to the subplate throughout cortical neurogenesis. Magnetic resonance imaging and histochemical studies show that the human subplate grows in size until the end of the second trimester. Previous microarray experiments in mice have shown several genes that are specifically expressed in the subplate layer of the rodent dorsal cortex. Here we examined the human subplate for some of these markers. In the human dorsal cortex, connective tissue growth factor-positive neurons can be seen in the ventricular zone at 15-22 postconceptional weeks (PCW) (most at 17 PCW) and are present in the subplate at 22 PCW. The nuclear receptor-related 1 protein is mostly expressed in the subplate in the dorsal cortex, but also in lower layer 6 in the lateral and perirhinal cortex, and can be detected from 12 PCW. Our results suggest that connective tissue growth factor-and nuclear receptor-related 1-positive cells are two distinct cell populations of the human subplate. Furthermore, our microarray analysis in rodent suggested that subplate neurons produce plasma proteins. Here we demonstrate that the human subplate also expresses a2zinc-binding globulin and Alpha-2-HeremansSchmid glycoprotein ⁄ human fetuin. In addition, the established subplate neuron marker neuropeptide Y is expressed superficially, whereas potassium ⁄ chloride co-transporter (KCC2)-positive neurons are localized in the deep subplate at 16 PCW. These observations imply that the human subplate shares gene expression patterns with rodent, but is more compartmentalized into superficial and deep sublayers. This increased complexity of the human subplate may contribute to differential vulnerability in response to hypoxia ⁄ ischaemia across the depth of the cortex. Combining knowledge of cell-type specific subplate gene expression with modern imaging methods will enable a better understanding of neuropathologies involving the subplate.

The development of the mammalian neocortex relies heavily on subplate. The proportion of this cell population varies considerably in different mammalian species. Subplate is almost undetectable in marsupials, forms a thin, but distinct layer in mouse and rat, a larger layer in carnivores and big-brained mammals as pig, and a highly developed embryonic structure in human and non-human primates. The evolutionary origin of subplate neurons is the subject of current debate. Some hypothesize that subplate represents the ancestral cortex of sauropsids, while others consider it to be an increasingly complex phylogenetic novelty of the mammalian neocortex. Here we review recent work on expression of several genes that were originally identified in rodent as highly and differentially expressed in subplate. We relate these observations to cellular morphology, birthdating, and hodology in the dorsal cortex/dorsal pallium of several amniote species. Based on this reviewed evidence we argue for a third hypothesis according to which subplate contains both ancestral and newly derived cell populations. We propose that the mammalian subplate originally derived from a phylogenetically ancient structure in the dorsal pallium of stem amniotes, but subsequently expanded with additional cell populations in the synapsid lineage to support an increasingly complex cortical plate development. Further understanding of the detailed molecular taxonomy, somatodendritic morphology, and connectivity of subplate in a comparative context should contribute to the identification of the ancestral and newly evolved populations of subplate neurons.