Systematizing and Cloning of Genes Involved in the Cerebellar Cortex Circuit Development

Furuichi, Teiichi; Shiraishi-Yamaguchi, Yoko; Sato, Akira; Sadakata, Tetsushi; Huang, Jinhong; Shinoda, Yo; Kanehiro, Hiromichi; Mishima, Yuriko; Tomomura, Mineko; Nishibe, Hirozumi; Yoshikawa, Fumio

doi:10.1007/s11064-011-0398-1

Cited by 16 publications

(18 citation statements)

References 61 publications

(95 reference statements)

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“…In cerebellar Purkinje cells, parallel fiber excitatory postsynaptic potentials are regulated by K channels and the Cav3.2 (Cacna1h) calcium channel [42]. The Cacng1 gene expressed in human fetal and adult brain [43] and developing mouse cerebellum [44]. A mutation of this gene was also proposed as a candidate for epilepsy [45] and its expression in hippocampal CA1 is altered in drug-induced epilepsy [46].…”

Section: Discussionmentioning

confidence: 99%

“…The remaining DE genes common to the three experimental groups were Cramp1l (alias: hematological and neurological expressed 1-like protein), which is a DNA and chromatin binding protein; Tada2b, a transcriptional adaptor protein; Lmod3, a fetally expressed member of the leiomodin family, which increases actin polymerization rate; Ndufaf2, which is NADH:ubiquinone oxidoreductase complex assembly factor 2; Sdr42e2, one of the short-chain dehydrogenases/reductases; and Unc45b, which acts as a co-chaperone for HSP90 and is required for the proper folding of the myosin motor domain [52]. These genes all have basic proliferation or differentiation functions, and expression of each was confirmed in the developing mouse cerebellum database [44] or the human brain database, GTEx Portal [53]. …”

Section: Discussionmentioning

confidence: 99%

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Neonicotinoid Insecticides Alter the Gene Expression Profile of Neuron-Enriched Cultures from Neonatal Rat Cerebellum

Kimura‐Kuroda

Nishito

Yanagisawa³

et al. 2016

IJERPH

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Neonicotinoids are considered safe because of their low affinities to mammalian nicotinic acetylcholine receptors (nAChRs) relative to insect nAChRs. However, because of importance of nAChRs in mammalian brain development, there remains a need to establish the safety of chronic neonicotinoid exposures with regards to children’s health. Here we examined the effects of long-term (14 days) and low dose (1 μM) exposure of neuron-enriched cultures from neonatal rat cerebellum to nicotine and two neonicotinoids: acetamiprid and imidacloprid. Immunocytochemistry revealed no differences in the number or morphology of immature neurons or glial cells in any group versus untreated control cultures. However, a slight disturbance in Purkinje cell dendritic arborization was observed in the exposed cultures. Next we performed transcriptome analysis on total RNAs using microarrays, and identified significant differential expression (p < 0.05, q < 0.05, ≥1.5 fold) between control cultures versus nicotine-, acetamiprid-, or imidacloprid-exposed cultures in 34, 48, and 67 genes, respectively. Common to all exposed groups were nine genes essential for neurodevelopment, suggesting that chronic neonicotinoid exposure alters the transcriptome of the developing mammalian brain in a similar way to nicotine exposure. Our results highlight the need for further careful investigations into the effects of neonicotinoids in the developing mammalian brain.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Neonicotinoid Insecticides Alter the Gene Expression Profile of Neuron-Enriched Cultures from Neonatal Rat Cerebellum

Kimura‐Kuroda

Nishito

Yanagisawa³

et al. 2016

IJERPH

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“…CGN cell bodies later migrate inwardly until reaching the internal granule cell layer (IGL), where postmigratory CGNs form mature dendrites and synaptic connections with input neurons. Numerous genes are sequentially expressed during these different developmental stages (Goldowitz and Hamre, 1998; Furuichi et al, 2011). Much of this developmental program is recapitulated in CGN cultures (Ito and Takeichi, 2009; de la Torre-Ubieta et al, 2010) wherein CGNPs and immature CGNs isolated from the EGL/PMZ (Raetzman and Siegel, 1999) differentiate into IGL-like cells upon plating (Manzini et al, 2006; Wang et al, 2011).…”

Section: Introductionmentioning

confidence: 99%

Temporal Regulation of Nuclear Factor One Occupancy by Calcineurin/NFAT Governs a Voltage-Sensitive Developmental Switch in Late Maturing Neurons

Ding¹,

Wang²,

Selvakumar³

et al. 2013

J. Neurosci.

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Dendrite and synapse development are critical for establishing appropriate neuronal circuits, and disrupted timing of these events can alter neural connectivity. Using microarrays, we have identified a nuclear factor I (NFI)-regulated temporal switch program linked to dendrite formation in developing mouse cerebellar granule neurons (CGNs). NFI function was required for upregulation of many synapse-related genes as well as downregulation of genes expressed in immature CGNs. Chromatin immunoprecipitation analysis revealed that a central feature of this program was temporally regulated NFI occupancy of late-expressed gene promoters. Developing CGNs undergo a hyperpolarizing shift in membrane potential, and depolarization inhibits their dendritic and synaptic maturation via activation of calcineurin (CaN) (Okazawa et al., 2009). Maintaining immature CGNs in a depolarized state blocked NFI temporal occupancy of late-expressed genes and the NFI switch program via activation of the CaN/nuclear factor of activated T-cells, cytoplasmic (NFATc) pathway and promotion of late-gene occupancy by NFATc4, and these mechanisms inhibited dendritogenesis. Conversely, inhibition of the CaN/NFATc pathway in CGNs maturing under physiological nondepolarizing conditions upregulated the NFI switch program, NFI temporal occupancy, and dendrite formation. NFATc4 occupied the promoters of late-expressed NFI program genes in immature mouse cerebellum, and its binding was temporally downregulated with development. Further, NFI temporal binding and switch gene expression were upregulated in the developing cerebellum of Nfatc4 (−/−) mice. These findings define a novel NFI switch and temporal occupancy program that forms a critical link between membrane potential/CaN and dendritic maturation in CGNs. CaN inhibits the program and NFI occupancy in immature CGNs by promoting NFATc4 binding to late-expressed genes. As maturing CGNs become more hyperpolarized, NFATc4 binding declines leading to onset of NFI temporal binding and the NFI switch program.

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“…BrainTx DB (http://www.cdtdb.neuroinf.jp) is a database for comprehensive ISH images of genes expressed in developing mouse brains (Furuichi et al 2011;Sato et al 2008). We used 2,810 ISH images from the young adult (3 weeks) mouse brain in this study.…”

Section: Methodsmentioning

confidence: 99%

“…Then, we compared the calculated intensities to expression intensity data of 3D maps within the coordinate space. In this study, we used three types of image data: (1) Waxholm space (WHS) datasets, which consist of mouse brain MR images along with a probabilistic atlas (Johnson et al 2010) as standard coordinates for transformation; (2) 2,810 ISH images of the mouse brain, within the BrainTx DB (http://www.cdtdb.neuroinf.jp) (Furuichi et al 2011;Sato et al 2008), as 2D ISH images that are transformed into the WHS; and (3) volume data of ViBrism DB gene expression 3D maps that are located within the WHS MR image space (http://vibrism.neuroinf.jp) (Okamura-Oho et al 2012. These ISH images exhibit high-resolution information in the X-Y plane, but few images are available for each gene.…”

Section: Introductionmentioning

confidence: 99%

Parallelized analysis of spatial gene expression patterns by database integration

Miyamoto

Ikeno²,

Okamura-Oho

et al. 2018

Preprint

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We developed a computational framework for automated integration of a large number of twodimensional (2D) images with three-dimensional (3D) image datasets located in the standard 3D coordinate. We applied the framework to 2,810 para-sagittal sectioned mouse brain 2D images of in situ hybridization (ISH), archived in the BrainTx database (http://www.cdtdb.neuroinf.jp). We registered the ISH images into the mouse standard coordinate space for MR images, Waxholm space (WHS, https://www.nitrc.org/projects/incfwhsmouse ) by linearly transforming them into each of a series of para-sagittal MR image slices, and identifying the best-fit slice by calculating the similarity metric value (). Transformed 2D images were compared with 3D gene expression image datasets, which were made using a microtomy-based microarray assay system, Transcriptome Tomography, and archived in the ViBrism DB (http://vibrism.neuroinf.jp): the 3D images are located in the WHS.We first transformed ISH images of 10 regionally expressed genes and compared them to signals of corresponding 3D expression images in ViBrism DB for evaluating the integration schema: two types of data, produced with different modalities and originally located in different dimensions, were successfully compared after enhancing ISH signals against background noise. Then, for the massive transformation of BrainTx database images, we parallelized our framework, using the IPython cluster package, and implemented it on the PC cluster provided for the Brain Atlasing Hackathon activity hosted by Neuroinformatics Japan Center in Japan. We could identify the best-fit positions for all of the ISH images. All programs were made available through the GitHub repository, at the web site of neuroinformatics/bah2016_registration (https://github.com/neuroinformatics/bah2016_registration).

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Systematizing and Cloning of Genes Involved in the Cerebellar Cortex Circuit Development

Cited by 16 publications

References 61 publications

Neonicotinoid Insecticides Alter the Gene Expression Profile of Neuron-Enriched Cultures from Neonatal Rat Cerebellum

Neonicotinoid Insecticides Alter the Gene Expression Profile of Neuron-Enriched Cultures from Neonatal Rat Cerebellum

Temporal Regulation of Nuclear Factor One Occupancy by Calcineurin/NFAT Governs a Voltage-Sensitive Developmental Switch in Late Maturing Neurons

Parallelized analysis of spatial gene expression patterns by database integration

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