Integrin α8β1 Is Critically Important for Epithelial–Mesenchymal Interactions during Kidney Morphogenesis

Müller, Ulrich; Wang, Denan; Denda, Sumiko; Meneses, Juanito J.; Pedersen, Roger A.; Reichardt, Louis F.

doi:10.1016/s0092-8674(00)81903-0

Cited by 345 publications

(321 citation statements)

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“…The linearized targeting vector was electroporated into JM1 embryonic stem cells (Muller et al, 1997) grown on mitotically inactivated STO cells. After 8 -10 d in selective medium (300 g /ml G418), colonies were picked, expanded, and screened for homologous recombination by Southern blotting using probes A and B as depicted in Figure 1 A.…”

Section: Methodsmentioning

confidence: 99%

The Role of Brain-Derived Neurotrophic Factor Receptors in the Mature Hippocampus: Modulation of Long-Term Potentiation through a Presynaptic Mechanism involving TrkB

et al. 2000

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The neurotrophin BDNF has been shown to modulate long-term potentiation (LTP) at Schaffer collateral-CA1 hippocampal synapses. Mutants in the BDNF receptor gene trkB and antibodies to its second receptor p75NTR have been used to determine the receptors and cells involved in this response. Inhibition of p75NTR does not detectably reduce LTP or affect presynaptic function, but analyses of newly generated trkB mutants implicate TrkB. One mutant has reduced expression in a normal pattern of TrkB throughout the brain. The second mutant was created by cre-loxP-mediated removal of TrkB in CA1 pyramidal neurons of this mouse. Neither mutant detectably impacts survival or morphology of hippocampal neurons. TrkB reduction, however, affects presynaptic function and reduces the ability of tetanic stimulation to induce LTP. Postsynaptic glutamate receptors are not affected by TrkB reduction, indicating that BDNF does not modulate plasticity through postsynaptic TrkB. Consistent with this, elimination of TrkB in postsynaptic neurons does not affect LTP. Moreover, normal LTP is generated in the mutant with reduced TrkB by a depolarization-low-frequency stimulation pairing protocol that puts minimal demands on presynaptic terminal function. Thus, BDNF appears to act through TrkB presynaptically, but not postsynaptically, to modulate LTP.

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Section: Methodsmentioning

confidence: 99%

The Role of Brain-Derived Neurotrophic Factor Receptors in the Mature Hippocampus: Modulation of Long-Term Potentiation through a Presynaptic Mechanism involving TrkB

et al. 2000

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“…Given the Arg-Gly-Asp motif-dependent interaction of QBRICK͞Frem1 with integrins such as ␣8␤1 (10), the stable deposition of QBRICK͞Frem1 at the basement membrane may be instrumental in mediating epithelial-mesenchymal interactions. In support of this possibility, renal agenesis has been reported in integrin ␣8-deficient mice (15). Alternatively, the stable deposition of QBRICK͞Frem1, Fras1, and Frem2 in the basement membrane may be necessary for the propagation of morphogenetic factor signals, as seen in the requirement of heparan sulfate chains by FGF for effective signal transduction through the FGF receptor (16).…”

Section: Reciprocal Requirement Of Qbrick͞frem1 For the Stable Basementmentioning

confidence: 97%

Breakdown of the reciprocal stabilization of QBRICK/Frem1, Fras1, and Frem2 at the basement membrane provokes Fraser syndrome-like defects

Kiyozumi

Sugimoto

Sekiguchi

2006

Proc. Natl. Acad. Sci. U.S.A.

111

178

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An emerging family of extracellular matrix proteins characterized by 12 consecutive CSPG repeats and the presence of Calx-␤ motif(s) includes Fras1, QBRICK͞Frem1, and Frem2. Mutations in the genes encoding these proteins have been associated with mouse models of Fraser syndrome, which is characterized by subepidermal blistering, cryptophthalmos, syndactyly, and renal dysmorphogenesis. Here, we report that all of these proteins are localized to the basement membrane, and that their basement membrane localization is simultaneously impaired in Fraser syndrome model mice. In Frem2 mutant mice, not only Frem2 but Fras1 and QBRICK͞Frem1 were depleted from the basement membrane zone. This coordinated reduction in basement membrane deposition was also observed in another Fraser syndrome model mouse, in which GRIP1, a Fras1-and Frem2-interacting adaptor protein, is primarily affected. Targeted disruption of Qbrick͞Frem1 also resulted in diminished expression of Fras1 and Frem2 at the epidermal basement membrane, confirming the reciprocal stabilization of QBRICK͞ Frem1, Fras1, and Frem2 in this location. When expressed and secreted by transfected cells, these proteins formed a ternary complex, raising the possibility that their reciprocal stabilization at the basement membrane is due to complex formation. Given the close association of Fraser syndrome phenotypes with defective epidermal-dermal interactions, the coordinated assembly of three Fraser syndrome-associated proteins at the basement membrane appears to be instrumental in epidermal-dermal interactions during morphogenetic processes.epithelial-mesenchymal interaction ͉ gene targeting ͉ morphogenesis T he extracellular matrix (ECM) is an insoluble supramolecular complex surrounding metazoan cells that is often fibrous or sheet-like. The ECM functions in the control of cellular behaviors, including migration, proliferation, and differentiation, and mediates intercellular communication, as in epithelialmesenchymal interactions; both of these functions are critical during development. Because individual ECM components often function in combination with other ECM components and soluble factors, genetic disorders of the ECM are often linked to severe developmental abnormalities.

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“…Alternatively, one of the other genes in the region could be the relevant target of loss. The NPNT/ LOC255743 gene, encoding an apparent orthologue of the mouse nephronectin gene, is another interesting candidate tumor suppressor, as nephronectin is an extracellular matrix component that is a ligand for a 8 /h 1 integrin, which is in turn a molecule that is essential for metanephric kidney maturation (40)(41)(42)(43)(44).…”

Section: Regions Of Recurrent Loh In Sporadic Wilms' Tumorsmentioning

confidence: 99%

Genomic Profiling Maps Loss of Heterozygosity and Defines the Timing and Stage Dependence of Epigenetic and Genetic Events in Wilms' Tumors

Yuan

Yamashiro³

et al. 2005

Molecular Cancer Research

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To understand genetic and epigenetic pathways in Wilms' tumors, we carried out a genome scan for loss of heterozygosity (LOH) using Affymetrix 10K single nucleotide polymorphism (SNP) chips and supplemented the data with karyotype information. To score loss of imprinting (LOI) of the IGF2 gene, we assessed DNA methylation of the H19 5V differentially methylated region (DMR). Few chromosomal regions other than band 11p13 (WT1) were lost in Wilms' tumors from Denys-Drash and Wilms' tumor-aniridia syndromes, whereas sporadic Wilms' tumors showed LOH of several regions, most frequently 11p15 but also 1p, 4q, 7p, 11q, 14q, 16q, and 17p. LOI was common in the sporadic Wilms' tumors but absent in the syndromic cases. The SNP chips identified novel centers of LOH in the sporadic tumors, including a 2.4-Mb minimal region on chromosome 4q24-q25. Losses of chromosomes 1p, 14q, 16q, and 17p were more common in tumors presenting at an advanced stage; 11p15 LOH was seen at all stages, whereas LOI was associated with early-stage presentation. Wilms' tumors with LOI often completely lacked LOH in the genome-wide analysis, and in some tumors with concomitant 16q LOH and LOI, the loss of chromosome 16q was mosaic, whereas the H19 DMR methylation was complete. These findings confirm molecular differences between sporadic and syndromic Wilms' tumors, define regions of recurrent LOH, and indicate that gain of methylation at the H19 DMR is an early event in Wilms' tumorigenesis that is independent of chromosomal losses. The data further suggest a biological difference between sporadic Wilms' tumors with and without LOI. (Mol Cancer Res 2005;3(9):493 -502)

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Integrin α8β1 Is Critically Important for Epithelial–Mesenchymal Interactions during Kidney Morphogenesis

Cited by 345 publications

References 50 publications

The Role of Brain-Derived Neurotrophic Factor Receptors in the Mature Hippocampus: Modulation of Long-Term Potentiation through a Presynaptic Mechanism involving TrkB

The Role of Brain-Derived Neurotrophic Factor Receptors in the Mature Hippocampus: Modulation of Long-Term Potentiation through a Presynaptic Mechanism involving TrkB

Breakdown of the reciprocal stabilization of QBRICK/Frem1, Fras1, and Frem2 at the basement membrane provokes Fraser syndrome-like defects

Genomic Profiling Maps Loss of Heterozygosity and Defines the Timing and Stage Dependence of Epigenetic and Genetic Events in Wilms' Tumors

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