Distribution of PCP4 protein in the forebrain of adult mice

Renelt, Maria; Halbach, Viola von Bohlen und; Halbach, Oliver von Bohlen und

doi:10.1016/j.acthis.2014.04.012

Cited by 20 publications

(14 citation statements)

References 27 publications

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“…One of the next challenges is to establish the identity of the X gene, which is necessary to understand the mechanism of Kcnj6-associated suppression. Among 16 Hsa21 gene orthologs in the Kcnj15-Mx2 region, Ets2, Psmg1, Brwd1, Hmgn1, Wrb, Pcp4 and Dscam are the potential candidates because they are well expressed in the brain (28)(29)(30)(31)(32)(33)(34)(35)(36)(37)(38). One of the approaches to identify the X gene is to compound a null allele of a candidate gene with Dp(16)1 and Df(16)7 simultaneously.…”

Section: Discussionmentioning

confidence: 99%

Genetic dissection of the Down syndrome critical region

Jiang

Liu

et al. 2015

Hum. Mol. Genet.

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Down syndrome (DS), caused by trisomy 21, is the most common chromosomal disorder associated with developmental cognitive deficits. Despite intensive efforts, the genetic mechanisms underlying developmental cognitive deficits remain poorly understood, and no treatment has been proven effective. The previous mouse-based experiments suggest that the so-called Down syndrome critical region of human chromosome 21 is an important region for this phenotype, which is demarcated by Setd4/Cbr1 and Fam3b/Mx2. We first confirmed the importance of the Cbr1-Fam3b region using compound mutant mice, which carry a duplication spanning the entire human chromosome 21 orthologous region on mouse chromosome 16 [Dp(16)1Yey] and Ms1Rhr. By dividing the Setd4-Mx2 region into complementary Setd4-Kcnj6 and Kcnj15-Mx2 intervals, we started an unbiased dissection through generating and analyzing Dp(16)1Yey/Df(16Setd4-Kcnj6)Yey and Dp(16)1Yey/Df(16Kcnj15-Mx2)Yey mice. Surprisingly, the Dp(16)1Yey-associated cognitive phenotypes were not rescued by either deletion in the compound mutants, suggesting the possible presence of at least one causative gene in each of the two regions. The partial rescue by a Dyrk1a mutation in a compound mutant carrying Dp(16)1Yey and the Dyrk1a mutation confirmed the causative role of Dyrk1a, whereas the absence of a similar rescue by Df(16Dyrk1a-Kcnj6)Yey in Dp(16)1Yey/Df(16Dyrk1a-Kcnj6)Yey mice demonstrated the importance of Kcnj6. Our results revealed the high levels of complexities of gene actions and interactions associated with the Setd4/Cbr1-Fam3b/Mx2 region as well as their relationship with developmental cognitive deficits in DS.

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Section: Discussionmentioning

confidence: 99%

Genetic dissection of the Down syndrome critical region

Jiang

Liu

et al. 2015

Hum. Mol. Genet.

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“…[1][2][3] The principal cells of the hilus, CA1, and CA3 are susceptible to excitotoxicity and epileptiform activity (EA), whereas the majority of dentate granule cells and CA2 pyramidal cells (PCs) are resistant to these detrimental impacts. 9,10 Recently, the termination of mossy fibers onto proximal dendrites of CA2 PCs has been demonstrated, 11 challenging the classical view of the trisynaptic circuit in the hippocampus. 9,10 Recently, the termination of mossy fibers onto proximal dendrites of CA2 PCs has been demonstrated, 11 challenging the classical view of the trisynaptic circuit in the hippocampus.…”

Section: Introductionmentioning

confidence: 99%

“…4 Remarkably, the two cell populations share characteristics, including a more negative resting potential compared to CA1 neurons, robust resistance toward induction of long-term potentiation, [5][6][7] high potassium conductance 7,8 and expression of the calmodulin signaling-regulating Purkinje cell protein 4 (PCP4). 9,10 Recently, the termination of mossy fibers onto proximal dendrites of CA2 PCs has been demonstrated, 11 challenging the classical view of the trisynaptic circuit in the hippocampus. Using the intrahippocampal kainate (KA) mouse model for MTLE, we found remarkable mossy fiber sprouting into CA2 with aberrant synapses surrounding CA2 PC somata.…”

Section: Introductionmentioning

confidence: 99%

Expression of brain‐derived neurotrophic factor and structural plasticity in the dentate gyrus and CA2 region correlate with epileptiform activity

2019

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Objective Hippocampal sclerosis is a hallmark of mesial temporal lobe epilepsy (MTLE), comprising gliosis and neuronal loss in the hippocampus. However, dentate granule cells and CA2 pyramidal cells (PCs) survive, as they share physiological characteristics that may render them less sensitive to hyperexcitation in MTLE. Here, we asked whether both engage similar molecular plasticity mechanisms to support their resilience in MTLE. We chose brain‐derived neurotrophic factor (BDNF), correlated the expression with activity, and used neuropeptide Y (NPY) and principal cell dispersion as plasticity readout. Methods Adult male mice received a unilateral intrahippocampal kainate injection to induce status epilepticus (SE) and bilateral electrodes into the dentate gyrus and CA2 for in vivo recordings and quantification of epileptiform activity. To assess the time course of Bdnf mRNA expression in these regions, we performed fluorescence in situ hybridization, complemented by immunohistochemistry for NPY and quantification of principal cell dispersion. Results We show that Bdnf expression was transiently up‐regulated during SE in the granule cell layer (GCL) and CA2 and, after a slight reduction at 2 days, increased persistently in both regions ipsilaterally. Intrahippocampal recordings revealed a threshold for the duration of SE to induce these changes. Recurrent epileptiform activity developed in the ipsilateral dentate gyrus and CA2 over time and was correlated with Bdnf mRNA levels, although more pronounced in the dentate gyrus. The dispersion of the GCL and CA2 correlated with Bdnf mRNA expression. NPY protein expression was only increased in granule cells and mossy fibers, remaining unchanged in CA2. Significance Our study reveals differential molecular plasticity changes in granule cells and CA2 PCs despite many similarities (epileptiform activity, somatic mossy fiber input, dispersion). These findings contribute to the understanding of common as well as individual characteristics of the cell populations underlying the epileptic hippocampal network.

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“…PCP4, one of the spatial marker genes in olfactory bulb ( Fig. 4a) and a gene functioning as calmodulin binding protein, is known to be highly expressed in olfactory bulb and present different level of protein expression in granule cell and mitral cell 11 layer 21 . Meanwhile, SLC12A1, also known as NKCC2 (Na-K-Cl cotransporter 2) is specifically expressed on thick ascending limb of Henle and located mainly in apical part of the cell 22 .…”

Section: Discussionmentioning

confidence: 99%

Discovery of molecular features underlying morphological landscape by integrating spatial transcriptomic data with deep features of tissue image

Bae

Choi

Lee

2020

Preprint

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Profiling molecular features associated with the morphological landscape of tissue is crucial to interrogate structural and spatial patterns that underlie biological function of tissues.Here, we present a new method, SPADE, to identify important genes associated with morphological contexts by combining spatial transcriptomic data with co-registered images.SPADE incorporates deep learning-derived image patterns with spatially resolved gene expression data to extract morphological context markers. Morphological features that correspond to spatial maps of transcriptome were extracted by image patches surrounding each spot, and then, represented by image latent features. The molecular profiles correlated with the image latent features were identified. The extracted genes could be further analyzed to discover functional terms and also exploited to extract clusters maintaining morphological contexts. We apply our approach to spatial transcriptomic data of three different tissues to suggest an unbiased method capable of offering image-integrated gene expression trends.

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Distribution of PCP4 protein in the forebrain of adult mice

Cited by 20 publications

References 27 publications

Genetic dissection of the Down syndrome critical region

Genetic dissection of the Down syndrome critical region

Expression of brain‐derived neurotrophic factor and structural plasticity in the dentate gyrus and CA2 region correlate with epileptiform activity

Discovery of molecular features underlying morphological landscape by integrating spatial transcriptomic data with deep features of tissue image

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