Absence of SPARC leads to impaired lens circulation

Greiling, Teri M.; Stone, Brad; Clark, John I.

doi:10.1016/j.exer.2009.04.008

Cited by 15 publications

(12 citation statements)

References 47 publications

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“…Mouse lens microarray datasets at various stages were obtained from NCBI GEO database or generated new in this study ( Supplementary Table S1 ) ( 1 , 7 , 9 , 12 , 27 – 33 ). These data on normal or specific gene-perturbation mouse lenses are on four different microarray platforms: Affymetrix 430 2.0; Affymetrix 430A 2.0; Illumina MouseWG-6 v1.0; Illumina MouseWG-6 v2.0.…”

Section: Methodsmentioning

confidence: 99%

iSyTE 2.0: a database for expression-based gene discovery in the eye

Kakrana

Yang

Anand

et al. 2017

Nucleic Acids Research

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Although successful in identifying new cataract-linked genes, the previous version of the database iSyTE (integrated Systems Tool for Eye gene discovery) was based on expression information on just three mouse lens stages and was functionally limited to visualization by only UCSC-Genome Browser tracks. To increase its efficacy, here we provide an enhanced iSyTE version 2.0 (URL: http://research.bioinformatics.udel.edu/iSyTE) based on well-curated, comprehensive genome-level lens expression data as a one-stop portal for the effective visualization and analysis of candidate genes in lens development and disease. iSyTE 2.0 includes all publicly available lens Affymetrix and Illumina microarray datasets representing a broad range of embryonic and postnatal stages from wild-type and specific gene-perturbation mouse mutants with eye defects. Further, we developed a new user-friendly web interface for direct access and cogent visualization of the curated expression data, which supports convenient searches and a range of downstream analyses. The utility of these new iSyTE 2.0 features is illustrated through examples of established genes associated with lens development and pathobiology, which serve as tutorials for its application by the end-user. iSyTE 2.0 will facilitate the prioritization of eye development and disease-linked candidate genes in studies involving transcriptomics or next-generation sequencing data, linkage analysis and GWAS approaches.

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Section: Methodsmentioning

confidence: 99%

iSyTE 2.0: a database for expression-based gene discovery in the eye

Kakrana

Yang

Anand

et al. 2017

Nucleic Acids Research

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“…These efforts have generated large expression datasets for normal and defective lens development (Agrawal et al, 2015; Anand et al, 2015; Audette et al, 2016; Chauhan et al, 2002a, 2002b; Chauss et al, 2014; De Maria and Bassnett, 2015; Greiling et al, 2009; Hawse et al, 2005, 2004, 2003; Hoang et al, 2014; Ivanov et al, 2005; Khan et al, 2016, 2015; Kumar et al, 2015; Lachke et al, 2012b, 2011; Manthey et al, 2014a; Sousounis et al, 2015, 2013; Sousounis and Tsonis, 2012; Wistow et al, 2002; Wolf et al, 2013b; Wride et al, 2003; Xiao et al, 2006). Although highly informative, early microarray studies used platforms representing only a subset of genes ( n =9,700) in the mouse genome (Chauhan et al, 2002a, 2002b).…”

Section: Genome-level Expression Profiling Of Lens Developmentmentioning

confidence: 99%

“…Microarray analysis of mouse mutant lenses of a post-transcriptional regulator gene Tdrd7 identified several DEGs including the heat shock protein Hspb1 (Hsp27) (Lachke et al, 2011), while microarrays on mouse lenses with a deletion in the matricellular glycoprotein gene Sparc showed altered expression of genes encoding matrix and adhesion proteins, cytoskeletal proteins and signaling molecules (Greiling et al, 2009). …”

Section: Genome-level Expression Profiling Of Lens Developmentmentioning

confidence: 99%

Systems biology of lens development: A paradigm for disease gene discovery in the eye

Anand

Lachke

2017

Experimental Eye Research

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Over the past several decades, the biology of the developing lens has been investigated using molecular genetics-based approaches in various vertebrate model systems. These efforts, involving target gene knockouts or knockdowns, have led to major advances in our understanding of lens morphogenesis and the pathological basis of cataracts, as well as of other lens related eye defects. In particular, we now have a functional understanding of regulators such as Pax6, Six3, Sox2, Oct1 (Pou2f1), Meis1, Pnox1, Zeb2 (Sip1), Mab21l1, Foxe3, Tfap2a (Ap2-alpha), Pitx3, Sox11, Prox1, Sox1, c-Maf, Mafg, Mafk, Hsf4, Fgfrs, Bmp7, and Tdrd7 in this tissue. However, whether these individual regulators interact or their targets overlap, and the significance of such interactions during lens morphogenesis, is not well defined. The arrival of high-throughput approaches for gene expression profiling (microarrays, RNA-sequencing (RNA-seq), etc.), which can be coupled with chromatin immunoprecipitation (ChIP) or RNA immunoprecipitation (RIP) assays, along with improved computational resources and publically available datasets (e.g. those containing comprehensive protein-protein, protein-DNA information), presents new opportunities to advance our understanding of the lens tissue on a global systems level. Such systems-level knowledge will lead to the derivation of the underlying lens gene regulatory network (GRN), defined as a circuit map of the regulator-target interactions functional in lens development, which can be applied to expedite cataract gene discovery. In this review, we cover the various systems-level approaches such as microarrays, RNA-seq, and ChIP that are already being applied to lens studies and discuss strategies for assembling and interpreting these vast amounts of high-throughput information for effective dispersion to the scientific community. In particular, we discuss strategies for effective interpretation of this new information in the context of the rich knowledge obtained through the application of traditional single-gene focused experiments on the lens. Finally, we discuss our vision for integrating these diverse high-throughput datasets in a single web-based user-friendly tool iSyTE (integrated Systems Tool for Eye gene discovery) – a resource that is already proving effective in the identification and characterization of genes linked to lens development and cataract. We anticipate that application of a similar approach to other ocular tissues such as the retina and the cornea, and even other organ systems, will significantly impact disease gene discovery.

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“…Smaller, more uniform collagen I fibrils are observed in the dermis of Sparc-null mice relative to wild-type mice. Within a few months, cataracts become visible in Sparc-null mice, a deformity hypothesized to be attributed in part to decreased collagen IV stability in lens capsules (Greiling et al 2009;Norose et al 1998). SPARC is enriched in basal laminae of Drosophila melanogaster embryos, and in the absence of SPARC collagen IV, incorporation is de-regulated, consistent with the finding of compromised collagen maturation and/or stability in Sparc-null mice (Martinek et al 2008;Rentz et al 2007).…”

Section: Introductionmentioning

confidence: 95%

Molecular evolution of SPARC: absence of the acidic module and expression in the endoderm of the starlet sea anemone, Nematostella vectensis

et al. 2009

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The matricellular glycoprotein SPARC is composed of three functional domains that are evolutionarily conserved in organisms ranging from nematodes to mammals: a Ca(2+)-binding glutamic acid-rich acidic domain at the N-terminus (domain I), a follistatin-like module (domain II), and an extracellular Ca(2+)-binding (EC) module that contains two EF-hands and two collagen-binding epitopes (domain III). We report that four SPARC orthologs (designated nvSPARC1-4) are expressed by the genome of the starlet anemone Nematostella vectensis, a diploblastic basal cnidarian composed of an ectoderm and endoderm separated by collagen-based mesoglea. We also report that domain I is absent from all N. vectensis SPARC orthologs. In situ hybridization data indicate that N. vectensis SPARC mRNAs are restricted to the endoderm during post-gastrula development. The absence of the Ca(2+)-binding N-terminal domain in cnidarians and conservation of collagen-binding epitopes suggests that SPARC first evolved as a collagen-binding matricellular glycoprotein, an interaction likely to be dependent on the binding of Ca(2+)-ions to the two EF-hands in the EC domain. We propose that further Ca(2+)-dependent activities emerged with the acquisition of an acidic N-terminal module in triplobastic organisms.

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Absence of SPARC leads to impaired lens circulation

Cited by 15 publications

References 47 publications

iSyTE 2.0: a database for expression-based gene discovery in the eye

iSyTE 2.0: a database for expression-based gene discovery in the eye

Systems biology of lens development: A paradigm for disease gene discovery in the eye

Molecular evolution of SPARC: absence of the acidic module and expression in the endoderm of the starlet sea anemone, Nematostella vectensis

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