Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0403608 (ureter)
 9,655 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Fgfrl1 is a novel member of the fibroblast growth factor receptor family. Its extracellular domain resembles the four conventional Fgfrs, while its intracellular domain lacks the tyrosine kinase domain necessary for Fgf mediated signal transduction. During embryonic development Fgfrl1 is expressed in the musculoskeletal system, in the lung, the pancreas and the metanephric kidney. Targeted disruption of the Fgfrl1 gene leads to the perinatal death of the mice due to a hypoplastic diaphragm, which is unable to inflate the lungs. Here we show that Fgfrl1-/- embryos also fail to develop the metanephric kidney. While the rest of the urogenital system, including bladder, ureter and sexual organs, develops normally, a dramatic reduction of ureteric branching morphogenesis and a lack of mesenchymal-to-epithelial transition in the nephrogenic mesenchyme result in severe renal dysgenesis. The failure of nephron induction might be explained by the absence of the tubulogenic markers Wnt4, Fgf8, Pax8 and Lim1 at E12.5 of the mutant animals. We also observed a loss of Pax2 positive nephron precursor cells and an increase of apoptosis in the cortical zone of the remnant kidney. Fgfrl1 is therefore essential for mesenchymal differentiation in the early steps of nephrogenesis.
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PMID:The murine Fgfrl1 receptor is essential for the development of the metanephric kidney. 1971 89

The Wnt4 gene encodes a secreted signaling molecule controlling the development of several organs, such as the kidney, adrenal gland, ovary, mammary gland and pituitary gland. It is thought to act in the embryonic kidney as an auto-inducer of nephrogenesis controlling mesenchyme-to-epithelium transition, and Wnt4-deficient mice die soon after birth, probably of kidney failure. Given the requirement for Wnt4 signaling in the control of organogenesis, the targeting of Cre recombinase under the control of the Wnt4 promoter would provide a valuable tool for fate mapping and functional genomics. We report here on the generation and characterization of a Wnt4(EGFPCre) knock-in allele where the EGFPCre fusion cDNA and Neo selection cassette were targeted into the Wnt4 locus. EGFP-derived fluorescence was observed in the pretubular aggregates of the E14.5 embryonic kidney that normally express Wnt4 mRNA. Characterization of the pattern of recombination of the floxed Rosa26(LacZ) reporter with the Wnt4(EGFPCre) allele revealed that in addition to the embryonic kidney, reporter-derived staining was observed in the embryonic gonad, spinal cord, lung and adrenal gland, i.e. the sites of Wnt4 gene expression. Time-lapse fate mapping of the Wnt4(EGFPCre)-activated yellow fluorescent protein (YFP) from the Rosa26 locus in organ culture revealed that the cells that had expressed the Wnt4 gene contributed to the nephrons, some of the cells around the stalk of the developing ureter and also certain presumptive medullary stromal cells. Moreover, the time-lapse movies suggested that the first few pretubular cell aggregates may not mature into nephrons but instead appear to disintegrate. In association with this, Rosa26(YFP)-positive stromal cells emerge around these disintegrating structures. Such cells may be transient, since their derivatives are neither detected later in the more mature kidney nor is there an overlap of the Wnt4(EGFPCre); Rosa26(LacZ)-marked cells with those of the endothelial cells, the smooth muscle cells or the macrophages. The Wnt4(EGFPCre) allele provides a useful new tool for conditional mutagenesis and provides the first time-lapse-based map of the fate of nephron precursor cells.
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PMID:Mapping of the fate of cell lineages generated from cells that express the Wnt4 gene by time-lapse during kidney development. 1974 May 93

Paired box2 (Pax2) gene plays a crucial role in kidney development and is expressed in the nephric duct, mesenchyme of pronephrons, mesonephrons, and metanephrons with special spatial and temporal characteristic. Research in animals indicate that Pax2 can interact with many important transcription factors such as Gdnf, Ret, SHH, Wnt4, and Fgf to organize the nephric linage specification, pro/mesonephric tubule formation and descent, emergence of the ureteric bud, branching morphogenesis, and nephron induction. Pax2 is associated with various congenital renal and ureter malformations, and the mutation is easist to detected in Renal-coloboma syndrome. In renal cell carcinoma, Wilms tumor and many acquired kidney diseases Pax2 is expressed abnormally, whose diagnose and therapy value will be the focus of further research. This paper reviews the molecular structure, expression and regulation of Pax2 in kidney development and diseases.
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PMID:[The role of Pax2 in regulation of kidney development and kidney disease]. 2195 93

The transcription factors HNF1B and Pax2, co-expressed in the Wolffian duct and ureteric bud epithelia, play essential roles during the early steps of mouse kidney development. In humans, heterozygous mutations in these genes display a number of common kidney phenotypes, including hypoplasia and multicystic hypoplastic kidneys. Moreover, a high prevalence of mutations either in HNF1B or PAX2 has been observed in children with renal hypodysplasia. To gain a better understanding of Hnf1b and Pax2 interactions in vivo, we generated compound heterozygous mice for Hnf1b and Pax2 null alleles. We show here that compound heterozygous mutants display phenotypes similar to severe congenital anomalies of the kidney and the urinary tract (CAKUT), including strong hypoplasia of the kidneys, caudal ectopic aborted ureter buds, duplex kidneys, megaureters and hydronephrosis. At a molecular level, compound mutants show a delay in nephron segment and medullar interstitial differentiation, increased apoptosis and a transient decrease in Lim1 and Wnt4 expression. We also observe a perturbation of smooth muscle differentiation around the ureter associated with a local down-regulation in transcript levels of Bmp4 and Tbx18, two key regulators involved in ureter smooth muscle formation, thus explaining, at least in part, megaureters. These results together uncover a novel role of Hnf1b as a modifier of the Pax2 haplo-insufficient phenotype and show that these two transcription factors operate in common pathways governing both kidney morphogenesis and ureter differentiation. This mouse model should provide new insights into the pathogenic mechanisms of human CAKUT, the most frequent developmental defect identified in newborns.
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PMID:Hnf1b and Pax2 cooperate to control different pathways in kidney and ureter morphogenesis. 2251 95