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A regulatory toolbox of MiniPromoters to drive selective expression in the brain.

ABSTRACT: The Pleiades Promoter Project integrates genomewide bioinformatics with large-scale knockin mouse production and histological examination of expression patterns to develop MiniPromoters and related tools designed to study and treat the brain by directed gene expression. Genes with brain expression patterns of interest are subjected to bioinformatic analysis to delineate candidate regulatory regions, which are then incorporated into a panel of compact human MiniPromoters to drive expression to brain regions and cell types of interest. Using single-copy, homologous-recombination "knockins" in embryonic stem cells, each MiniPromoter reporter is integrated immediately 5' of the Hprt locus in the mouse genome. MiniPromoter expression profiles are characterized in differentiation assays of the transgenic cells or in mouse brains following transgenic mouse production. Histological examination of adult brains, eyes, and spinal cords for reporter gene activity is coupled to costaining with cell-type-specific markers to define expression. The publicly available Pleiades MiniPromoter Project is a key resource to facilitate research on brain development and therapies.

SUBMITTER: Portales-Casamar E

PROVIDER: S-EPMC2944712 | biostudies-literature | 2010 Sep

REPOSITORIES: biostudies-literature

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A regulatory toolbox of MiniPromoters to drive selective expression in the brain.

Portales-Casamar Elodie E Swanson Douglas J DJ Liu Li L de Leeuw Charles N CN Banks Kathleen G KG Ho Sui Shannan J SJ Fulton Debra L DL Ali Johar J Amirabbasi Mahsa M Arenillas David J DJ Babyak Nazar N Black Sonia F SF Bonaguro Russell J RJ Brauer Erich E Candido Tara R TR Castellarin Mauro M Chen Jing J Chen Ying Y Cheng Jason C Y JC Chopra Vik V Docking T Roderick TR Dreolini Lisa L D'Souza Cletus A CA Flynn Erin K EK Glenn Randy R Hatakka Kristi K Hearty Taryn G TG Imanian Behzad B Jiang Steven S Khorasan-zadeh Shadi S Komljenovic Ivana I Laprise Stéphanie S Liao Nancy Y NY Lim Jonathan S JS Lithwick Stuart S Liu Flora F Liu Jun J Lu Meifen M McConechy Melissa M McLeod Andrea J AJ Milisavljevic Marko M Mis Jacek J O'Connor Katie K Palma Betty B Palmquist Diana L DL Schmouth Jean-François JF Swanson Magdalena I MI Tam Bonny B Ticoll Amy A Turner Jenna L JL Varhol Richard R Vermeulen Jenny J Watkins Russell F RF Wilson Gary G Wong Bibiana K Y BK Wong Siaw H SH Wong Tony Y T TY Yang George S GS Ypsilanti Athena R AR Jones Steven J M SJ Holt Robert A RA Goldowitz Daniel D Wasserman Wyeth W WW Simpson Elizabeth M EM

Proceedings of the National Academy of Sciences of the United States of America 20100831 38

The Pleiades Promoter Project integrates genomewide bioinformatics with large-scale knockin mouse production and histological examination of expression patterns to develop MiniPromoters and related tools designed to study and treat the brain by directed gene expression. Genes with brain expression patterns of interest are subjected to bioinformatic analysis to delineate candidate regulatory regions, which are then incorporated into a panel of compact human MiniPromoters to drive expression to br ...[more]

PMID: 20807748

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Project description:Aim. In recent years, connectivity studies using neuroimaging data have increased the understanding of the organization of large-scale structural and functional brain networks. However, data analysis is time consuming as rigorous procedures must be assured, from structuring data and pre-processing to modality specific data procedures. Until now, no single toolbox was able to perform such investigations on truly multimodal image data from beginning to end, including the combination of different connectivity analyses. Thus, we have developed the Multimodal Imaging Brain Connectivity Analysis (MIBCA) toolbox with the goal of diminishing time waste in data processing and to allow an innovative and comprehensive approach to brain connectivity. Materials and Methods. The MIBCA toolbox is a fully automated all-in-one connectivity toolbox that offers pre-processing, connectivity and graph theoretical analyses of multimodal image data such as diffusion-weighted imaging, functional magnetic resonance imaging (fMRI) and positron emission tomography (PET). It was developed in MATLAB environment and pipelines well-known neuroimaging softwares such as Freesurfer, SPM, FSL, and Diffusion Toolkit. It further implements routines for the construction of structural, functional and effective or combined connectivity matrices, as well as, routines for the extraction and calculation of imaging and graph-theory metrics, the latter using also functions from the Brain Connectivity Toolbox. Finally, the toolbox performs group statistical analysis and enables data visualization in the form of matrices, 3D brain graphs and connectograms. In this paper the MIBCA toolbox is presented by illustrating its capabilities using multimodal image data from a group of 35 healthy subjects (19-73 years old) with volumetric T1-weighted, diffusion tensor imaging, and resting state fMRI data, and 10 subjets with 18F-Altanserin PET data also. Results. It was observed both a high inter-hemispheric symmetry and an intra-hemispheric modularity associated with structural data, whilst functional data presented lower inter-hemispheric symmetry and a high inter-hemispheric modularity. Furthermore, when testing for differences between two subgroups (<40 and >40 years old adults) we observed a significant reduction in the volume and thickness, and an increase in the mean diffusivity of most of the subcortical/cortical regions. Conclusion. While bridging the gap between the high numbers of packages and tools widely available for the neuroimaging community in one toolbox, MIBCA also offers different possibilities for combining, analysing and visualising data in novel ways, enabling a better understanding of the human brain.

Dataset Information

A regulatory toolbox of MiniPromoters to drive selective expression in the brain.

Publications

A regulatory toolbox of MiniPromoters to drive selective expression in the brain.

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