BackgroundCellular differentiation programs are controlled, to a large extent, by the combinatorial functioning of specific transcription factors. Cortical projection neurons constitute the major excitatory neuron population within the cortex and mediate long distance communication between the cortex and other brain regions. Our understanding of effector transcription factors and their downstream transcriptional programs that direct the differentiation process of cortical projection neurons is far from complete.ResultsIn this study, we carried out a ChIP-Seq (chromatin-immunoprecipitation and sequencing) analysis of NEUROD2, an effector transcription factor expressed in lineages of cortical projection neurons during the peak of cortical excitatory neurogenesis. Our results suggest that during cortical development NEUROD2 targets key genes that are required for Reelin signaling, a major pathway that regulates the migration of neurons from germinal zones to their final layers of residence within the cortex. We also find that NEUROD2 binds to a large set of genes with functions in layer-specific differentiation and in axonal pathfinding of cortical projection neurons.ConclusionsOur analysis of in vivo NEUROD2 target genes offers mechanistic insight into signaling pathways that regulate neuronal migration and axon guidance and identifies genes that are likely to be required for proper cortical development.Electronic supplementary materialThe online version of this article (doi:10.1186/s12864-015-1882-9) contains supplementary material, which is available to authorized users.

Calcium signaling controls many key processes in neurons, including gene expression, axon guidance, and synaptic plasticity. In contrast to calcium influx through voltage- or neurotransmitter-gated channels, regulatory pathways that control store-operated calcium entry (SOCE) in neurons are poorly understood. Here, we report a transcriptional control of Stim1 (stromal interaction molecule 1) gene, which is a major sensor of endoplasmic reticulum (ER) calcium levels and a regulator of SOCE. By using a genome-wide chromatin immunoprecipitation and sequencing approach in mice, we find that NEUROD2, a neurogenic transcription factor, binds to an intronic element within the Stim1 gene. We show that NEUROD2 limits Stim1 expression in cortical neurons and consequently fine-tunes the SOCE response upon depletion of ER calcium. Our findings reveal a novel mechanism that regulates neuronal calcium homeostasis during cortical development.

The fabrication of polymeric thin fi lms amenable to facile functionalization by reactive μ CP via a Diels-Alder reaction is described. Precursor copolymers containing FuMA, PEGMA, and TMSMA are prepared using ATRP. Surface-tethered thin fi lms of these polymers are obtained on oxidized silicon and glass substrates and patterned with maleimide-appended dye molecules by simple μ CP to demonstrate effi cient functionalization via Diels-Alder reaction. Printing of biotin-based ligands is carried out to demonstrate directed immobilization of the enzyme streptavidin. Due to the thermoreversible nature of the Diels-Alder reaction, these surfaces can be used as rewritable platforms. This is demonstrated by sequential write-erase-rewrite protocols via μ CP of a maleimide-containing fl uorescent dye.reactions have been utilized to date toward effi cient functionalization of appropriately modifi ed solid substrates. The Cu-catalyzed Huisgen [3 + 2] reaction is perhaps the most utilized one, but other "click" reactions such as the thiol-ene and Diels-Alder reactions are drawing attention due to their metal-free nature. Among the later reactions, the Diels-Alder reaction provides an attractive alternative due to the following attributes: (1) appropriate choice of diene and dienophile provides products in good yields in a highly predictable manner, (2) the reaction could be conducted in aqueous medium or neat without harsh chemical conditions, (3) most often no additional reagents or catalysts are required, and (4) reaction is thermoreversible. [ 3 ] As mentioned in the last point, this conjugationdeconjugation reaction harbors several reaction systems which could be irreversible or reversible over different temperature ranges based upon the molecular structure of the diene-dienophile pair. [ 4 ] Specifi cally, the maleimidefuran-based systems have attracted immense attention because of the "self-healing" feature that allows the fabrication of remendable materials. [ 5 ] To date, most of the efforts in the area of surface functionalization using the Diels-Alder reaction have focused on the modifi cation of self-assembled monolayers on

Activation of the leptin receptor, LepRb, by the adipocytokine/neurotrophic factor leptin in the central nervous system has procognitive and antidepressive effects. Leptin has been shown to increase glutamatergic synaptogenesis in multiple brain regions. In contrast, mice that have a mutation in the LepRb gene show abnormal synapse development in the hippocampus as well as deficits in cognition and increased depressive-like symptoms. Leptin increases glutamatergic synaptogenesis, in part, through enhancement of N-methyl-D-aspartic acid (NMDA) receptor function; yet the underlying signaling pathway is not known. In this study, we examine how leptin regulates surface expression of NR2B-containing NMDA receptors in hippocampal neurons. Leptin stimulation increases NR2BY1472 phosphorylation, which is inhibited by the Src family kinase inhibitor, PP1. Moreover, we show that Fyn, a member of the Src family kinases, is required for leptin-stimulated NR2BY1472 phosphorylation. Furthermore, inhibiting Y1472 phosphorylation with either a dominant negative Fyn mutant or an NR2B mutant that lacks the phosphorylation site (NR2BY1472F) blocks leptin-stimulated synaptogenesis. Additionally, we show that LepRb forms a complex with NR2B and Fyn. Taken together, these findings expand our knowledge of the LepRb interactome and the mechanisms by which leptin stimulates glutamatergic synaptogenesis in the developing hippocampus. Comprehending these mechanisms is key for understanding dendritic spine development and synaptogenesis, alterations of which are associated with many neurological disorders.