Screen for genes regulated during early kidney morphogenesis

Leimeister, Cornelia; Bach, Alexandra; Woolf, Adrian S.; Gessler, Manfred

doi:10.1002/(sici)1520-6408(1999)24:3/4<273::aid-dvg10>3.0.co;2-3

Cited by 20 publications

(13 citation statements)

References 27 publications

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“…We have applied DD to one critical morphogenetic event in this process, namely the epithelial conversion of metanephric mesenchyme. Others have used DD to characterize molecularly the complete inductive process, including early events, by comparing uninduced mesenchyme with induced tubular explants (Leimeister et al, 1999). This approach presumably detects genes regulated during condensation of mesenchyme as well and thus presents a more complicated picture of gene regulation than the current one.…”

Section: Discussionmentioning

confidence: 99%

“…The ␤1 subunit readily forms heterodimers with a variety of ␣ monomers and is expressed in several renal tissues, making ␤1 integrins the principal forms in the developing and mature kidney (for review, see Hamerski et al, 1999). Integrin-␣6 was previously shown to be up-regulated during differentiation of kidney epithelium (Leimeister et al, 1999;Falk et al, 1996). Integrin-mediated cell attachment activates diverse signaling pathways that can change cellular morphology as well as modulate gene expression and regulate cell proliferation, differentiation, and survival (for review, see Perantoni, 1999).…”

Section: Discussionmentioning

confidence: 99%

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Mesenchymal-epithelial transition in the developing metanephric kidney: Gene expression study by differential display

Plisov

Ivanov

Yoshino

et al. 2000

genesis

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The developing metanephric kidney is a convenient model to study molecular events associated with epithelial cell differentiation. To determine the genes involved in the defining event of this process, namely, the conversion of metanephric mesenchyme to the epithelium of the nephron, we applied differential display (DD) techniques. Explants of rat metanephric mesenchymes were induced to condense ex vivo with fibroblast growth factor 2 (FGF2) or to form tubules with FGF2 and conditioned medium (CM) from a cell line (RUB1) of ureteric bud, the renal inductive tissue. Three time points (6, 24, and 72 h) were chosen to track the dynamics of gene expression during morphogenesis. Seventy-two up- or down-regulated mRNAs were identified, including 36 novel sequences and those of cell cycle regulatory proteins (TGF-beta2, Cyclin D1, p57Kip2), transcription factors (beta-catenin, Sox11, DP1), signaling proteins (SH3-domain binding protein, G-protein-coupled receptor, Ser-Thr protein kinase), cell adhesion molecules (syndecan-4, integrin-beta1), and also gene33, H19, SM20, IGFBP5, MAMA receptor, lectin, keratin, beta-tubulin, calreticulin, GRP78, ERp72, MnSoD, thioredoxin, and others. Some have previously been associated with kidney development and serve as good controls for expected changes, while most have not been linked with kidney epithelial cell differentiation. Using thin sections of embryonic kidney and labeled antisense RNA probes, we applied RNA hybridization to confirm the results of DD and related the expression of these genes to specific cell lineages of the developing kidney. These results provide a window into the events that mediate this critical differentiation process and suggest that a limited number of interrelated events direct the epithelial conversion of metanephric mesenchyme. genesis 27:22-31, 2000. Published 2000 Wiley-Liss, Inc.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Mesenchymal-epithelial transition in the developing metanephric kidney: Gene expression study by differential display

Plisov

Ivanov

Yoshino

et al. 2000

genesis

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“…This final cleavage releases the Notch intracellular domain (ICN1), which is a transcription factor. Transport of ICN1 to the nucleus allows it to bind to other transcriptional activators, including RBP-Jk, MAML, p300 and the complex then mediates the transcription of various proteins including Hes and Hey family members, which are transcription factors by themselves to mediate the program of cell identity (Figure 1) (18), (19-21). In the absence of ICN1, RBP-Jk binds to a number of co-repressor molecules that repress transcription from the DNA bound to RBP-Jk (22).…”

Section: Podocyte Depletion In Renal Diseasementioning

confidence: 99%

The Pathogenic Role of Notch Activation in Podocytes

Niranjan

Murea²,

Suszták³

2009

Nephron Exp Nephrol

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Podocytes play a key role in the maintenance of the glomerular filtration barrier. Depletion or dysregulative mechanisms of podocytes can lead to the development of glomerulosclerosis. Signaling pathways that control these processes in podocytes are not fully understood. Recent studies from our and other laboratories found that genes that belong to the Notch pathway are regulated in patients and in animal models of renal disease. Genetic studies performed on mice with conditional expression of active Notch1 protein showed massive albuminuria, glomerulosclerosis, and ultimately renal failure and death of the animals. γ-Secretase inhibitors and genetic deletion of Notch transcriptional binding partner (Rbpj) protected animals from nephrotic syndrome. Further studies are needed to define whether the activation of Notch pathway in podocytes represents a common pathomechanism in glomerular injury, and its potential to be a therapeutic target for the treatment of chronic kidney disease.

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“…The asymmetric expression of the Notch ligand Dll1 in the distal domain of the renal vesicle and its persistence in the medial portion of the S-shaped bodies and the enrichment of Notch signaling components and targets in the proximal domain of the S-shaped bodies [21][22][23][24][25] raise the possibility that Notch signaling is involved in nephron segmentation. Mammals express four different Notch genes, Notch 1 to 4, all of which are type I transmembrane proteins with an extracellular ligand-binding domain and an intracellular domain that regulates transcription.…”

Section: Regional Expression Of Transcription Factors Along the Proximentioning

confidence: 99%

Molecular Insights into Segmentation along the Proximal–Distal Axis of the Nephron

Kopan¹,

Cheng²,

Surendran³

2007

Journal of the American Society of Nephrology

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Screen for genes regulated during early kidney morphogenesis

Cited by 20 publications

References 27 publications

Mesenchymal-epithelial transition in the developing metanephric kidney: Gene expression study by differential display

Mesenchymal-epithelial transition in the developing metanephric kidney: Gene expression study by differential display

The Pathogenic Role of Notch Activation in Podocytes

Molecular Insights into Segmentation along the Proximal–Distal Axis of the Nephron

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