Expression of Plxdc2/TEM7R in the developing nervous system of the mouse

Miller, Suzanne F.C.; Summerhurst, Kristen; Rünker, Annette E.; Kerjan, Géraldine; Friedel, Roland H.; Chédotal, Alain; Murphy, Paula; Mitchell, Kevin J.

doi:10.1016/j.modgep.2006.12.002

Cited by 42 publications

(49 citation statements)

References 23 publications

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“…39,40 At present, however, no functional significance is implied for this intergenic SNP, though a possibility can be speculated. This SNP is perfectly correlated (r 2 ¼ 1) with rs78099346 and rs1412557, which are, according to the ENCODE project data, 41,42 located in an early-replication domains where chromosomal DNA replication initiates earlier than other chromosomal regions in embryonic stem cells.…”

Section: Discussionmentioning

confidence: 92%

Expansive marker analysis replicating the association of glaucoma susceptibility with human chromosome loci 1q43 and 10p12.31

et al. 2013

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Three human chromosome loci (1q43, 10p12.31, and 12q21.31) were recently associated with the susceptibility to primary open-angle glaucoma (POAG) in a Japanese population; however, this was not replicated in three subsequent studies using South Indian, Afro-Caribbean, and Chinese populations. To identify genetic markers that are robustly associated across ethnic populations, numerous markers in addition to the six in the three reported loci were examined in this study. A total of 31 single-nucleotide polymorphism (SNP) markers were genotyped for 1115 Korean participants, and many neighboring SNPs were imputed using the Korean HapMap Project genotype data. Each SNP was statistically tested for association with POAG susceptibility by comparisons among 211 POAG patients with 904 unaffected controls. A strong and statistically significant association was found with a previously unreported SNP, rs7098387 (odds ratio, OR ¼ 2.0 (1.4-3.0), P ¼ 0.00038) at the 10p12.31 locus (where 11 SNPs were typed and 38 imputed) in contrast to the reported rs7081455, which was too poorly correlated with newly associated rs7098387 (r 2 ¼ 0.003, D 0 ¼ 0.40) to show association. Additionally, a modest association was observed with the reported rs693421 (OR ¼ 1.4 (1.1-1.7), P ¼ 0.0082) and several other SNPs located within and around ZP4 at the 1q43 locus (10 SNPs typed and 14 imputed). However, no association was observed with the reported rs7961953 SNP or any other SNPs at the 12q21.31 locus, upstream of TMTC2 (10 SNPs typed and 29 imputed). Accordingly, POAG susceptibility association was replicated using rs7098387 (C) rather than rs7081455 (T) at the 10p12.31 locus and additionally with rs693421 (T) at the 1q43 locus.

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Section: Discussionmentioning

confidence: 92%

Expansive marker analysis replicating the association of glaucoma susceptibility with human chromosome loci 1q43 and 10p12.31

et al. 2013

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“…It has been shown to regulate neuronal cell fate and proliferation. Interestingly, the ectodomain itself is sufficient for the observed effects on neurogenesis (45). BACE1 could thus control the function of this protein by regulating its cell surface levels as well as the amount and distribution of soluble, functional ectodomains.…”

Section: Discussionmentioning

confidence: 99%

Label-free Quantitative Proteomics of Mouse Cerebrospinal Fluid Detects β-Site APP Cleaving Enzyme (BACE1) Protease Substrates In Vivo

Dislich

Wohlrab

Bachhuber

et al. 2015

Molecular & Cellular Proteomics

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Analysis of murine cerebrospinal fluid (CSF) by quantitative mass spectrometry is challenging because of low CSF volume, low total protein concentration, and the presence of highly abundant proteins such as albumin. We demonstrate that the CSF proteome of individual mice can be analyzed in a quantitative manner to a depth of several hundred proteins in a robust and simple workflow consisting of single ultra HPLC runs on a benchtop mass spectrometer. The workflow is validated by a comparative analysis of BACE1؊/؊ and wild-type mice using label-free quantification. The protease BACE1 cleaves the amyloid precursor protein (APP) as well as several other substrates and is a major drug target in Alzheimer's disease. We identified a total of 715 proteins with at least 2 unique peptides and quantified 522 of those proteins in CSF from BACE1؊/؊ and wild-type mice. Several proteins, including the known BACE1 substrates APP, APLP1, CHL1 and contactin-2 showed lower abundance in the CSF of BACE1؊/؊ mice, demonstrating that BACE1 substrate identification is possible from CSF. Additionally, ectonucleotide pyrophosphatase 5 was identified as a novel BACE1 substrate and validated in cells using immunoblots and by an in vitro BACE1 protease assay. Likewise, receptor-type tyrosine-protein phosphatase N2 and plexin domain-containing 2 were confirmed as BACE1 substrates by in vitro assays. Taken Cerebrospinal fluid (CSF) 1 consists of interstitial fluid that is in continuous exchange with the central nervous system and the peripheral blood system. It represents the only body fluid in humans that is in direct contact with brain tissue and accessible in a routine clinical setting. Thus, the easy accessibility from the periphery renders CSF perfectly suited to study pathologic neurological processes (1). Human CSF has a relatively low protein content (ϳ 0.4 mg/ml), but features a highly diverse proteome. It is thus increasingly studied by modern mass spectrometry based proteomics (2). The proteomic analysis of human CSF typically involves various protein concentration and fractionation steps as well as the depletion of highly abundant proteins, such as serum albumin. This allows the identification of several hundred up to 2600 proteins from several milliliters of human CSF (3).Mice are the most popular animal model in preclinical research, because of their similarity to humans in genetics and physiology, their unlimited supply and their ease of genetic engineering. The study of their CSF can provide valuable insights into disease mechanisms and biomarker discovery Author Contributions: The manuscript was written by Bastian Dislich and Stefan F. Lichtenthaler. The study was guided and planned by Bastian Dislich, Sebastian Hogl, Melanie Meyer-Luehmann and Stefan F. Lichtenthaler. Bastian Dislich established the mass spectrometry of murine CSF and performed the proteomic analysis of the BACE1Ϫ/Ϫ CSF. Felix Wohlrab performed all other experiments, except for the CSF extraction, which was performed by Teresa Bachhuber, and the analysis of...

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“…Of the 24 000 genes examined, we focused on those that contribute to differentiation or development (Table 1). Key genes for the regulation of embryonic organogenesis (Hoxa5, Hoxa9, Foxc1 and Foxf2) and the commitment of immature cells to multiple lineages (Pparg, Cebpa, Plxnd1, Egfl7, Mgp, Plxdc2, Ebf1 and Tcf3) were expressed at higher levels in AO cells than in AX cells, suggesting that AO cells have characteristics of immature mesenchymal cells (Wang and Reed, 1993;Luo et al, 1997;Wu et al, 1999;Rosen et al, 2000;Parker et al, 2004;Torres-Vazquez et al, 2004;Miller et al, 2007;Cole et al, 2008). The profile of AX cells, on the other hand, was indicative of both cells that are committed to the osteocyte lineage (Dlx3, Sp7, Dkk1, Ostn and Bmp3) and cells that are inclined to tumorigenesis in vivo (Cd276, Ptgs2, Vegfa, Epha2, Frzb and Sfrp1) (Kim et al, 1993;Daluiski et al, 2001;Dannenberg et al, 2001;Thomas et al, 2003;Lee et al, 2004 Zang et al, 2007;Brantley-Sieders et al, 2008;Engin et al, 2008;Li et al, 2008).…”

Section: Ao and Ax Cells Differ In Their Gene Expression Profilesmentioning

confidence: 99%

c-MYC overexpression with loss of Ink4a/Arf transforms bone marrow stromal cells into osteosarcoma accompanied by loss of adipogenesis

et al. 2010

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The development of cancer is due to the growth and proliferation of transformed normal cells. Recent evidence suggests that the nature of oncogenic stress and the state of the cell of origin critically affect both tumorigenic activity and tumor histological type. However, this mechanistic relationship in mesenchymal tumors is currently largely unexplored. To clarify these issues, we established a mouse osteosarcoma (OS) model through overexpression of c-MYC in bone marrow stromal cells (BMSCs) derived from Ink4a/Arf (À/À) mice. Single-cell cloning revealed that c-MYC-expressing BMSCs are composed of two distinctly different clones: highly tumorigenic cells, similar to bipotent-committed osteochondral progenitor cells, and low-tumorigenic tripotent cells, similar to mesenchymal stem cells (MSCs). It is noteworthy that both bipotent and tripotent cells were capable of generating histologically similar, lethal OS, suggesting that both committed progenitor cells and MSCs can become OS cells of origin. Shifting mesenchymal differentiation by depleting PPARc in tripotent MSC-like cells and overexpressing PPARc in bipotent cells affected cell proliferation and tumorigenic activity. Our findings indicate that differentiation potential has a key role in OS tumorigenic activity, and that the suppression of adipogenic ability is a critical factor for the development of OS.

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Expression of Plxdc2/TEM7R in the developing nervous system of the mouse

Cited by 42 publications

References 23 publications

Expansive marker analysis replicating the association of glaucoma susceptibility with human chromosome loci 1q43 and 10p12.31

Expansive marker analysis replicating the association of glaucoma susceptibility with human chromosome loci 1q43 and 10p12.31

Label-free Quantitative Proteomics of Mouse Cerebrospinal Fluid Detects β-Site APP Cleaving Enzyme (BACE1) Protease Substrates In Vivo

c-MYC overexpression with loss of Ink4a/Arf transforms bone marrow stromal cells into osteosarcoma accompanied by loss of adipogenesis

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