CDT-DB Cerebellar Development transcriptome(CDT)

About CDT

 The Laboratory for Molecular Neurogenesis at the RIKEN Brain Science Institute is exploring spatiotemporal gene expression during the postnatal development of the mouse cerebellum to elucidate the genetic basis of cerebellar development. We have developed a database, the Cerebellar Development Transcriptome Database (CDT-DB), in which spatiotemporal gene expression profile data obtained by RT-PCR, microarray and in situ hybridization analyses are systematized in a searchable format with links to relevant bioinformatics sites. The CDT-DB project is supported by the RIKEN Brain Science Institute and the Neuroinformatics Japan Center (NIJC) that is the Japan Node of the International Neuroinformatics Coordinating Facility (INCF).

Contents

CDT-DB Project

1-1. Objectives

 The basic design for the brain, which is a very complex structure, must be encoded in the genome, and is attributable to the controlled expression of thousands of specific genes in time and space. To decipher the genetic blueprint for mouse cerebellar development, the Cerebellar Development Transcriptome Database (CDT-DB) project was launched in the Laboratory for Molecular Neurogenesis, RIKEN Brain Science Institute in 1999. The CDT-DB systematizes spatiotemporal gene expression in the mouse cerebellum during postnatal development.

1-2. Cerebellar postnatal development

 The cerebellum is a hindbrain region that coordinates gait and voluntary movement, is responsible for balance and posture, and is important in speech and control of gaze. We focus on the mouse cerebellum, which develops into a functional circuit and architecture (Fig. 1) during the postnatal three-week period through a series of magnificent cellular developmental events (Fig. 2).

 Granule cells (GCs), the sole excitatory neurons in the cerebellar circuit, are generated by the vigorous proliferation of granule cell progenitors (GCPs) in the external germinal (or granular) layer (EGL) during the first two weeks after birth. This proliferation leads to an immense number of cells, accounting for approximately half of the neurons in the mammalian brain. Post-mitotic GCs then bilaterally extend their parallel fiber (PF) axons, and their cell bodies start to migrate downward through the developing molecular layer (ML), eventually settling in the internal granular layer (IGL) underneath the Purkinje cell layer (PCL). The EGL is divided into two sub-layers: the outer EGL (oEGL) containing proliferating GPCs and the inner EGL (iEGL) containing nascent post-mitotic GCs.

 During these first three weeks, cells in the pia matter (PM) play a role in GC proliferation and migration, whereas Bergmann glia (BG) processes extending into the ML appear to guide GCs. GCs that reach the IGL further differentiate, and extend their dendrites into glomeruli in which GCs connect excitatory afferent mossy fibers (MFs) and inhibitory Golgi cell (Go) axons. A portion of the GC population in the EGL undergoes cell death (apoptosis), which is thought to occur to fine-tune the proper cell numbers and connectivity. During these GC events, Purkinje cells (PCs), the principle neurons of the cerebellar circuit, undergo a robust outgrowth of their dendrites and form elaborate arborizations on which PCs receive two excitatory inputs from PFs and climbing fibers (CFs). Distal spiny dendrites of PCs have numerous spines, and each spine forms a synaptic connection with an extending PF. Large proximal dendrites of PCs form synapses with CFs that are pruned away from multiple (at an early stage) to mono (at late stage) innervation in an activity-dependent manner. PC axons are the sole output from the cerebellar cortex to the cerebellar nuclei (CN) (or deep cerebellar nuclei, DCN). These developmental events involving GCs and PCs are mutually regulated by synergistic actions between GCs and PCs.

 Three types of inhibitory interneurons, stellate cells (St), basket cells (Ba) and Golgi cells (Go), proliferate and then migrate during the first or second postnatal week to their proper positions-the outer two-thirds of the ML, the inner third of the ML, and the upper IGL, respectively-where they each form specific local connections (St and Ba, feed-forward pathways from PFs to PCs; Go, a feedback pathway from PFs to GCs) by the third postnatal week. Other minor interneurons, such as unipolar brush cells and Lugaro cells, are not indicated in Fig. 1 (see Fig. 1 on the "ISH Atlas" page). Oligodendrocytes (Od) proliferate and differentiate in the white matter (WM). Myelination starts to appear from P3 in the central deep WM and progresses in the WM of the folia in the first and second postnatal weeks, whereas that of PC axons in the IGL starts to appear by P10 and progresses by the third postnatal week. Astrocytes (As) and other cells are thought to play some roles in these cerebellar developmental events.

1-3. Cerebellar development transcriptome (CDT)

Fig. 3. A functional network of the CD genes involved in the cell cycle and proliferation of granule cells.  →  Click on the image to enlarge it.

 The genetic blueprint for cerebellar development should be mirrored in the cerebellar development transcriptome (CDT), a set of all transcription events during cerebellar development. In order for this series of postnatal development events to proceed smoothly, expression of specific genes and gene groups must be controlled in a timely way at each developmental stage. Assuming these genes are expressed in an orderly fashion on a developmental timetable, we formulated the idea that genes crucial to a series of these events could be efficiently identified by genome-wide analysis of gene expression at each developmental stage using fluorescent differential display (FDD) and DNA microarray (GeneChip and CDT array) techniques. In addition to this developmental time series, providing temporal gene expression profiling data, we spatially map gene expression on the developing cerebellar cortex circuit by in situ hybridization (ISH) brain histochemistry to profile spatial cellular gene expression. These spatiotemporal gene expression profile data are annotated by citing pre-defined annotation terms (see 2-2-2) and by classifying data based on the developmental and anatomical context (see 2-2-4) (also see 4. Publication-1, Sato et al., 2008).

 At present, the CDT-DB includes a list of cerebellar development (CD) genes and their integrated spatiotemporal expression profiles during postnatal cerebellar development. To decipher the genetic blueprint for cerebellar development, it will be necessary to further elucidate the gene cascades involved in each event. Figure 3 illustrates a functional network of CD gene products involved in granule cell proliferation. Most of the CD genes listed here were identified as part of the CDT-DB project (genes written in black), and thus can be found by searching the CDT-DB. Besides the listed genes, many others are involved in the cell cycle and proliferation of granule cell progenitors, and will be compiled in the CDT-DB in the future. After that, transcriptional regulation cascades for each gene or gene group will be elucidated so that the complete genetic blueprint (GenBlueprint) for cerebellar development can emerge.

1-4. Privacy Policy

 We will not attempt to collect your personal information when you visit this website; moreover, if you email us, we will respond to your email, but will not otherwise retain or distribute your email address. We provide links to other websites providing additional information about the data compiled in the CDT-DB. Once you link to another site, you are subject to the privacy policy of that site.

1-5. Copyright

 The RIKEN Brain Science Institute makes no representation about the suitability or accuracy of this software or data for any purpose, and makes no warranties, either expressed or implied, about the merchantability or fitness of the software or data for a particular purpose. RIKEN makes no claim that the use of this software or data will not infringe on any third-party patents, copyrights, trademarks, or other rights. The software and data, which are provided as-is, are intended to enhance knowledge and encourage progress in the scientific community; they are to be used for research and educational purposes only. Any reproduction or use for commercial purposes is prohibited without the prior express written permission of the RIKEN Brain Science Institute. We are not responsible for the copyright of any information provided in sites to which we provide links. Copyright (C) by RIKEN BSI, Japan. All rights reserved.

1-6. How to create URL links to the CDT-DB

 We recommend that you use the following syntax to create a URL link to the CDT-DB gene information page via CD ID number.

     http://www.cdtdb.brain.riken.jp/CDT/ReferCDInformation.do?cdid=CDxxxxx&from=External

where xxxxx is a CD ID number (numerals of 5 digits).

Example
To create a URL link to the gene information page for "CD00002", put "00002" between "cdid=CD" and "&from=External"

     http://www.cdtdb.brain.riken.jp/CDT/ReferCDInformation.do?cdid=CD00002&from=External

1-7. Acknowledgments

 The CDT-DB project is supported by the RIKEN Brain Science Institute and the Neuroinformatics Japan Center (NIJC), which is the Japan Node of the International Neuroinformatics Coordinating Facility (INCF). The CDT-DB includes many lines of valuable information from the relevant public bioinformatics databases, and contains hyperlinks to these websites. We gratefully appreciate these databases: MGI (Jackson Lab.), Ensembl (Sanger Inst/EBI), Entrez Nucleotide (NCBI), UniGene (NCBI), Entrez Gene (NCBI), OMIM (NCBI), GEO (NCBI), KEGG (Kyoto Univ.), Gene Ontology (OBO), Harvester (Karlsruhe Inst. of Tech.), UCSC Mouse Genome Browser Gateway (UC Santa Cruz), Perlegen/NIEHS Mouse Genome Browser (NIEHS), GeneNetwork (Univ. of Tennessee), Mouse Phenome Database (Jackson Lab.), SymAtlas (Genomics Inst. of Novartis Res. Foundation), STRING (EMBL/SIB/UZH), SynDB (Peking Univ.), Mouse Neuronal Expression Database (Brandeis Univ.), GoPubMed (Technische Univ. Dresden), iHOP (Memorial Sloan-Kettering Cancer Center), PubMed (NCBI), ABA (Allen Inst. for Brain Sci.), GenePaint (Max Planck Inst.), BGEM (St. Jude children's Res. Hospital), and Affymetrix.

1-8. Contact Information

 If you have questions or comments about the CDT-DB, please contact us at:

CDT-DB

2-0. Notes

Note 1: Although some digital image data may not be of the highest quality, all data registered here are representative and are the most readily reproducible images we have obtained thus far. Digital images will be updated as they become available (2-1).

Note 2: Because the FDD-derived, genome-hit CD clones marked with "Int" (intron sequence), "5'End" (5'-upstream sequence), or "3'End" (3'-downstream sequence) are provisional, we leave their gene descriptions up to the judgment of users (2-2-2). These FDD clones might be derived from non-coding RNAs and/or undefined exon sequences that are produced by alternative splicing events during cerebellar development.

Note 3: Some CD genes that show only slight developmental changes in their expression levels by our conventional semi-quantitative RT-PCR or GeneChip analyses are categorized for now into the "almost constant" regulation type, since more accurate methods are needed to determine the precise degree of change. The temporal patterns of some genes differ slightly depending on the method used, possibly due to differences in sensitivity between methods and other technical variations (2-2-4).

Note 4: ISH images of some CD genes, including even known genes, show nuclear staining patterns (mostly nucleoli), which may be due to either hybridization with unspliced RNAs or unknown causes (2-2-4).

2-1. About the CDT-DB

 To elucidate the cerebellar development transcriptome (CDT), we are exploring differential expression of cerebellar development genes (CD genes) during the postnatal development of the mouse cerebellum by utilizing genome-wide gene expression analysis approaches, such as fluorescence differential display (FDD), cDNA microarray (CDT array) and GeneChip analyses. The temporal expression patterns of some CD genes are further analyzed by semi-quantitative reverse transcription-polymerase chain reaction (RT-PCR). The spatial expression patterns of CD genes are analyzed by in situ hybridization (ISH) brain histochemistry. The brain specificity of gene expression is being determined by RT-PCR or GeneChip analyses. We have systematized the spatiotemporal CD gene expression profile information and generated an integrative CDT-DB that can be used with Web browsers (see "Help" for how to use the CDT-DB). The CDT-DB features various search functions for CD genes and their spatiotemporal expression profiles, and provides easy accessibility to relevant public bioinformatics database websites.

 In the CDT-DB, we intend to provide researchers with nearly raw data of our experiments (RT-PCR gel images, ISH brain images, and microarray diagrams) in formats that are familiar to most neuroscience researchers, so that users will be able to benefit from the CDT-DB immediately.
Note: Although some digital image data may not be of the highest quality, all data registered here are representative and reproducible. Digital images will be updated when improved data are obtained.

 We hope that the CDT-DB will be of some help to researchers who are concerned with the molecular basis of brain development and disorders.

2-2. Information about cerebellar development (CD) genes

1. Cerebellar development (CD) genes and their identification number (CD ID)

 CD genes are identified from mouse cerebellum tissue (ICR or C57B/6J) using FDD and GeneChip analyses, as described above.

 The CD ID (CD plus five numerals: example CD98765) is the identification number assigned to each CD gene. Some CD genes have been detected and analyzed by multiple approaches.

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2. Gene name, gene description, alternative name

 We have assigned gene symbols, gene descriptions and alternative names to CD genes by referring to the Entrez Gene, UniGene, MGI, and Ensembl databases.

 Although a fraction of the ESTs (expressed sequence tags) identified by the FDD analysis do not match any cDNA or EST sequences, but do match known genomic sequences, many of these FDD clones correspond to sequences within introns, 3'-flanking regions, and 5'-flanking regions of known genes. We thus assume that some of these are derived from alternatively spliced mRNAs, differentially terminated or initiated mRNAs, nuclear pre-mRNAs, or noncoding small RNAs (see also 2-0 Note 2). In the CDT-DB, such ESTs are provisionally annotated as follows:

Int: within the intron of a corresponding known gene
3'End (predicted): within the 3'-flanking region of a corresponding known gene
5'End (predicted): within the 5'-flanking region of a corresponding known gene

 Here, we restrict the predicted flanking regions within, at most, 2.5 kb from either the 5' or the 3' ends of known genes. In any case, it should be noted that because the FDD-derived, genome-hit CD clones marked "Int", "5'End", or "3'End" are provisional, we leave their gene description up to the judgment of users.

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3. Gene category

 The CD genes are classified into 34 gene categories according to the structural and functional properties of the gene products (encoded proteins), by referring to their annotations in the literature and/or to the terms used to describe them in the MGI and Gene Ontology (GO).

4. Expression profiles

 Timetabling of gene expression was carried out by developmental RT-PCR, GeneChip, and custom-made cDNA microarray (CDT array) analyses. Cellular mapping of gene expression was conducted by ISH analysis. Brain specificity of gene expression was estimated by tissue-specific RT-PCR and GeneChip analyses. The names of mouse strains analyzed (ICR or C57B/6J) are indicated on the expression information pages.

 Temporal expression indicates developmental gene expression patterns determined by RT-PCR, GeneChip and CDT array analyses using RNA sources prepared from developing cerebella (RT-PCR and CDT array; E18, P0, P3, P7, P12, P15, P21, and P56) (GeneChip; E18, P7, P14, P21, and P56). Note: Some CD genes that show only slight developmental changes in their expression levels by our conventional semi-quantitative RT-PCR are categorized for now into the "almost constant" expression pattern type, since more accurate methods are needed to determine the precise degree of change The temporal patterns of some genes differ slightly according to the methods used, which may be due to differences in sensitivity between methods or other technical differences.

 Spatial expression and Brain distribution indicate cellular expression patterns in cerebella and regional distribution patterns in brains, respectively, evaluated by in situ hybridization (ISH) analysis of P7 and P21 mice. Note: ISH images of some CD genes, including even known genes, show nuclear staining patterns (mostly nucleoli), which may be due to hybridization with unspliced RNAs or to unknown causes.

 Brain specificity indicates tissue distribution patterns determined by RT-PCR or GeneChip analyses using RNA sources from eight different tissues. For RT-PCR analysis, RNAs at either P7 or P21, depending on which stage shows a higher expression level, were used, whereas for GeneChip analysis RNAs from mice at both P7 and P21 were used.

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5. EST sequences

 The DNA sequences of all ESTs identified in this CDT-DB project were registered to the DNA Data Bank of Japan (DDBJ) and are available by accession number (BP426256-BP428449) from DDBJ/GenBank/Embl.

6. Links

 The CDT-DB includes easy links to relevant bioinformatics database sites. Thus, one can easily access additional information about most CD genes through these links. EST sequence information: Nucleotide. General information: MGI, Ensembl, UniGene, Entrez Gene, OMIM, GEO, KEGG. Genome information: Harvester, UCSC Mouse Genome Browser Gateway, Perlegen/NIEHS Mouse Genome Browser. Functional genomics: GeneNetwork, Mouse Phenome Database, SymAtlas, STRING. Nervous system: SynDB, Mouse Neuronal Expression Database. Reference information: GoPubMed, iHOP, PubMed (NCBI). Spatial information: ABA, GenePaint, BGEM. Array information: Affymetrix.

7. References

 To complement the gene annotation information, the CDT-DB lists papers selected by us and cited by relevant databases, and contains links to PubMed.

2-3. Search for CD genes and spatiotemporal gene expression patterns

 In the CDT-DB, users can search for CD genes based on gene names/symbols, protein structures, and functions using the Gene Search function. CD genes can be listed based on their specificity in spatiotemporal expression patterns by using the following Expression Search Menu, and selected genes may be added to My List (for details about the use of the database, see "Help").

Temporal expression: Select CD genes based on developmental regulation types. (Press the Legend button for an explanation of abbreviation).

DN: down-regulation	AC: almost constant expression
UP: up-regulation	P: pending classification
UD: up-and-down regulation

Spatial expression: Select CD genes based on specifically or dominantly expressed cerebellar layers or cell type at P7 and P21. (Press the Legend button for an explanation of abbreviation).

Layers

PM: pia matter	PCL: Purkinje cell layer
oEGL: outer EGL (external germinal or granular layer)	IGL: internal granular layer
iEGL: inner EGL (external germinal or granular layer)	WM: white matter
ML: molecular layer

Cell types

St: stellate cell	BG: Bergmann glia
Ba: basket cell	Od: oligodendrocyte
PC: Purkinje cell	CN: cerebellar nuclei (deep cerebellar nuclei, DCN)
GC: granule cell	As: astrocyte
Go: Golgi cell	other: other cell

Brain distribution: Select CD genes by specifically or dominantly expressed brain regions at P7 and P21. (Press the Legend button for explanation of abbreviation).

Ob: olfactory bulb	Tc: tectum
Cx: cerebral cortex	Tg: tegmentum
Bg: basal ganglia	Cb: cerebellum
Hi: hippocampus	Po: pons
Th: thalamus	Me: medulla oblongata
Hy: hypothalamus	Other: other region

Brain specificity: Select CD genes by brain specificity or dominancy in comparison with seven other tissues (thymus, lung, heart, liver, spleen, kidney, testis) at P7 or P21. (Press the Legend button for an explanation).

Information about the gene expression profiling data

3-1. Fluorescent differential display (FDD) analysis

 We analyzed mRNA expression in ICR mouse cerebella during postnatal developmental (stages E18, P0, P3, P7, P12, P15, P21, and P56) by FDD. DNase-treated total RNAs isolated from each stage were subjected to RT-PCR in duplicate, using combinations of arbitrary primers (10-mer) and FITC-labeled anchor poly-d(T) primers (GT(15)X; X = A, C, or G), followed by gel electrophoresis under non-denaturing conditions. FITC-labeled bands with differential developmental patterns were visualized using a fluorescent image scanner (Molecular Imager FX, Bio-Rad Laboratories) and were excised from gels, followed by cloning into TA-cloning vectors such as pCR4-TOPO (Invitrogen). One-run DNA sequencing analysis of about 12,000 FDD clones was carried out at the facilities of the RIKEN Genomic Sciences Center (in collaboration with the Genome Sequencing Team). As a result of BLAST searches, about 2,000 nonredundant FDD clones were identified. It should be noted that some FDD clones contain sequences outside the exons of known or predicted genes, for example, introns, the 5'-flanking region, and the 3'-flanking region, as described above, although RNA samples were treated with RNase-free DNase to remove contaminated chromosomal DNAs.

3-2. cDNA microarray (CDT array) analysis

 We generated a custom-made cDNA microarray (named "CDT array") spotted with about 2,400 genes that were either represented by the FDD clones or known to be involved in cerebellar development. We applied CDT array analysis to parallel monitoring of the expression of these CD genes during cerebellar development (stages E18, P0, P3, P7, P12, P15, P21, and P56) in mice (ICR). Hybridization was carried out using probes labeled with Cy3 and Cy5 (CyScribe, Amersham). Digital images of hybridization were acquired using a laser scanner (GenePix4000A, Axon Instruments) and analyzed with bioinformatics software (Acuity 3.1, Axon Instruments, or GeneSpring GX v10, Agilent). In the CDT-DB, the CDT array data are available in graphical formats showing the expression profiles of single genes or groups of genes within gene categories. We also analyzed gene expression profiles in the cerebella of five spontaneous mutant mice, Lurcher, Purkinje cell degeneration (pcd), reeler, staggerer, and weaver, data on which will be updated in the future.

3-3. Affymetrix GeneChip analysis

 Developmental time series GeneChip analysis- We first analyzed gene expression profiles during cerebellar development of ICR mice (E18, P7, P14, P21, and P56) by utilizing the GeneChip system (Affymetrix Mu11K, 12,654 probes, including known mouse genes and ESTs). We found that 10,321 probes (81.6%) were expressed in one of the developmental stages, and that 8.7% of these (897/10,321) showed apparent differential expression during development, in which the difference between the highest and lowest expression signals was more than two-fold (see 4. Publication-3, Kagami and Furuichi, 2001). In the CDT-DB, we have compiled GeneChip data, including data on five additional probe genes (for a total of 902), in graphical formats of single genes or groups of genes within gene categories.
 Some of these data are also available in the NCBI Gene Expression Omnibus (GEO) (Platform GPL8, Series GSE2, and Sample GSM50, GSM51, GSM52, GSM53, and GSM54).

• GPL8
• GSE2
• GSM50
• GSM51
• GPL52
• GSM53
• GSM54

 To increase coverage for the detection of the CDT, we recently utilized the Affymetrix Mouse Genome 430 2.0 Array, including probes for about 39,000 transcripts, for the analysis of C57BL/6J mice. As a result, approximately 7,100 probes were identified as differentially expressed during cerebellar development (see 4. Publication-1, Sato et al., 2008).

 Tissue specific GeneChip analysis- To estimate the brain specificity of gene expression, we utilized the Affymetrix Mouse Genome 430A 2.0 Array, including probes for approximately 15,000 transcripts, and analyzed RNAs from eight different tissues (brain, thymus, lung, heart, liver, spleen, kidney, and testis) of mice (C57BL/6J) at P7 or P21.

3-4. RT-PCR analysis

 Developmental time series RT-PCR- We analyzed the developmental time series expression patterns of CD genes by a conventional semi-quantitative RT-PCR method using ExTaq polymerase (Takara), cerebellar cDNAs of eight developmental stages (E18, P0, P3, P7, P12, P15, P21, and P56), and CD gene-specific primer sets (18-25 mer) at 20-35 cycles in a GeneAmp9700 thermal cycler (PerkinElmer). After agarose gel electrophoresis, PCR products were stained with EtBr, and digital images of banding patterns were acquired using a fluorescent image scanner (Molecular Imager FX, Bio-Rad Laboratories). RT-PCR profiles were tested by multiple experiments (some were tested more than ten times), using different RNA or cDNA sources, or using different primer sets or reaction conditions (temperature, Mg²⁺ concentration, etc.), depending on the consistency of the banding patterns.

 

 Tissue specific RT-PCR- The brain specificity (tissue distribution) of CD gene expression was also analyzed by RT-PCR using cDNAs prepared from RNAs obtained from eight mouse tissues (brain, thymus, lung, heart, liver, spleen, kidney, and testis) at P7 or P21, as described above.

3-5. In situ hybridization (ISH) analysis

 The spatial cellular expression patterns of the CD genes were analyzed by in situ hybridization (ISH) histochemistry of P7 and P21 mouse brains (ICR or C57BL/6J). Sagittal paraffin sections (6 µm) were prepared using an automated paraffin sample preparation instrument (Tissue-Tek tissue processor and tissue embedding console IV, Sakura) and a rotary microtome with a sampling apparatus (MICROM HM 335E). After proteinase K digestion, hybridization was carried out in a solution containing 4x SSC, 50% formamide, 0.5 mg/ml yeast tRNA, 1x Denhardt's solution, 5 mM EDTA, and digoxigenin (DIG)-UTP (Roche)-labeled riboprobes at 60-65°C. Probes hybridized with mRNAs were detected by staining with anti-DIG antibody (Roche) and NBT/BCIP (Roche). At least two sections prepared from different brain positions were analyzed for each ISH reaction. ISH profiles for each CD gene were generally examined several times, if necessary by changing experimental conditions (temperature, probe or antibody concentration, hybridization or staining time).

 In addition to the manual methods described above, we utilized an automated ISH experiment system, Freedom EVO GenePaint (TECAN), developed by Dr. Gregor Eichele's Laboratory at the Max Planck Institute and Bayer College of Medicine, Germany. Some of our ISH data were obtained using this TECAN ISH apparatus and a protocol modified for paraffin sections and regular DIG labeling method without tyramide signal amplification.

 Digital images of hybridized sections were acquired using a Nikon E800 microscope equipped with a Spot Insight QE-cooled CCD camera, an Olympus BX51 microscope equipped with a ProgRes C14 cooled CCD camera, and a stereoscopic microscope (Nikon SMZ-U) equipped with a CCD camera (Spot Insight). To obtain high-resolution images of whole mouse brains, we utilized a digital slide scanner NanoZoomer Digital Pathology (NDP; Hamamatsu Photonics K.K.). These high resolution brain images are used to display magnified images in two viewer functions, "Detailed view" and "Simple zoom" (see "Help"). If necessary, digital images were adjusted as little as possible using Adobe Photoshop CS2 software to normalize some of the differences (for example, in color, contrast, or scanning noise and moire) that often occur during digitization.

Publications regarding the CDT-DB

Copyright (C) by RIKEN BSI, Japan. All rights reserved. Updated: April 2, 2009. CDT-DB Ver.4.1