Expression and localization of fibroblast growth factors and fibroblast growth factor receptors in the developing rat kidney

Cancilla, Belinda; Ford-Perriss, Miriam; Bertram, John F.

doi:10.1046/j.1523-1755.1999.00781.x

Cited by 64 publications

(53 citation statements)

References 47 publications

(6 reference statements)

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“…On the other hand, genes underexpressed in Wilms tumors tend to be expressed higher in differentiated structures (such as glomerulus or nephron) than in MM or its early differentiating derivatives (such as blastema or condensates). These genes include Lim-1, PDGFA, BMP7, VEGF, CDH1, CDH6, COL4A1, COL4A2, COL5A1, COL5A2 and ITGA2 (all identified from the kidney development database) and AGT (Niimura et al, 1997), SDC1 (Cook et al, 1996), TYRO10/DDR2 (Stuart et al, 2003), FGFR3 (Cancilla et al, 1999), frizzled homolog 1 (FZD1) (Lechner and Dressler, 1997), c-myc (Harding et al, 1992), TGFA (Diaz-Ruiz et al, 1993), TGFBR2 (Wang et al, 1995) and THBS1 (Kang et al, 2001) (Supplementary Table 1) (Figure 2).…”

Section: Gene Expression Connection Between Wilms Tumorigenesis and Kmentioning

confidence: 99%

Transcript profiling of Wilms tumors reveals connections to kidney morphogenesis and expression patterns associated with anaplasia

Kessler

Williams

2004

Oncogene

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Anaplasia (unfavorable histology) is associated with therapy resistance and poor prognosis of Wilms tumor, but the molecular basis for this phenotype is unclear. Here, we used a cDNA array with 9240 clones relevant to cancer biology and/or kidney development to examine the expression profiles of 54 Wilms tumors, five normal kidneys and fetal kidney. By linking genes differentially expressed between fetal kidney and Wilms tumors to kidney morphogenesis, we found that genes expressed at a higher level in Wilms tumors tend to be expressed more in uninduced metanephrogenic mesenchyme or blastema than in their differentiated structures. Conversely, genes expressed at a lower level in Wilms tumors tend to be expressed less in uninduced metanephrogenic mesenchyme or blastema. We also identified 97 clones representing 76 Unigenes or unclustered ESTs that clearly separate anaplastic Wilms tumors from tumors with favorable histology. Genes in this set provide insight into the nature of the abnormal nuclear morphology of anaplastic tumors and may facilitate identification of molecular targets to improve their responsiveness to treatment.

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Section: Gene Expression Connection Between Wilms Tumorigenesis and Kmentioning

confidence: 99%

Transcript profiling of Wilms tumors reveals connections to kidney morphogenesis and expression patterns associated with anaplasia

Kessler

Williams

2004

Oncogene

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“…FGFR3 is normally expressed in the tissues of the central nervous system, brain, kidney and testis, but not in the spleen, heart or muscle (Cancilla et al, 1999;Plowright et al, 2000). Missense mutations in the transmembrane region of FGFR3 result in constitutive activation and the autosomal dominant heritable disorders of skeletal development such as thanatophoric dwarfism, achondroplasia and Crouzon syndrome (Tavormina et al, 1995;Naski et al, 1996;Bonaventure et al, 2001).…”

mentioning

confidence: 99%

FGFR3IIIS: a novel soluble FGFR3 spliced variant that modulates growth is frequently expressed in tumour cells

Merrick

2003

Br J Cancer

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Fibroblast growth factor receptor 3 (FGFR3) is one of four high-affinity tyrosine kinase receptors for the FGF family of ligands, frequently associated with growth arrest and induction of differentiation. The extracellular immunoglobulin (IgG)-like domains II and III are responsible for ligand binding; alternative usage of exons IIIb and IIIc of the Ig-like domain III determining the ligand-binding specificity of the receptor. By reverse transcriptase polymerase chain reaction (RT -PCR) a novel FGFR3IIIc variant FGFR3IIIS, expressed in a high proportion of tumours and tumour cell lines but rarely in normal tissues, has been identified. Unlike recently described nonsense transcripts of FGFR3, the coding region of FGFR3IIIS remains in-frame producing a novel protein. The protein product is coexpressed with FGFR3IIIc in the membrane and soluble cell fractions; expression in the soluble fraction is decreased after exposure to bFGF but not aFGF. Knockout of FGFR3IIIS using antisense has a growth-inhibitory effect in vitro, suggesting a dominantnegative function for FGFR3IIIS inhibiting FGFR3-induced growth arrest. In summary, alternative splicing of the FGFR3 Ig-domain III represents a mechanism for the generation of receptor diversity. FGFR3IIIS may regulate FGF and FGFR trafficking and function, possibly contributing to the development of a malignant phenotype.

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“…Although Fgfr3 and Fgfr4 have been detected in embryonic kidneys [13][14][15], Fgfr1, Fgfr2, and Fgfrl1 appear to be the most relevant receptors regarding renal development (see below). Fgfr1 is expressed most prominently in rodent mesenchymal tissues (early metanephric mesenchyme, condensing mesenchyme, and developing nephrons), but is present at lower levels in the ureteric lineage and in renal cortical stroma [16][17][18][19][20].…”

Section: Background On Kidney Development and Fibroblast Growth Factomentioning

confidence: 99%

“…Fgfr1 is expressed most prominently in rodent mesenchymal tissues (early metanephric mesenchyme, condensing mesenchyme, and developing nephrons), but is present at lower levels in the ureteric lineage and in renal cortical stroma [16][17][18][19][20]. Fgfr2 is strongly expressed in the Wolffian duct and the ureteric bud tree (tips and trunks) and differentiating nephrons, but is present at lower levels in early MM and stromal mesenchyme adjacent to the Wolffian duct and main ureteric trunk [13,[16][17][18][19][20]. Fgfrl1 is present in renal vesicles [12].…”

Section: Background On Kidney Development and Fibroblast Growth Factomentioning

confidence: 99%

Role of fibroblast growth factor receptor signaling in kidney development

Bates

2007

Pediatr Nephrol

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Fibroblast growth factor receptors (Fgfrs) are expressed throughout the developing kidney. Several early studies have shown that exogenous fibroblast growth factors (Fgfs) affect growth and maturation of the metanephric mesenchyme (MM) and ureteric bud (UB). Transgenic mice that overexpress a dominant negative receptor isoform develop renal aplasia/severe dysplasia, confirming the importance of Fgfrs in renal development. Furthermore, global deletion of Fgf7, Fgf10, and Fgfr2IIIb (isoform that binds Fgf7 and Fgf10) in mice leads to small kidneys with fewer collecting ducts and nephrons. Deletion of Fgfrl1, a receptor lacking intracellular signaling domains, causes severe renal dysgenesis. Conditional targeting of Fgf8 from the MM interrupts nephron formation. Deletion of Fgfr2 from the UB results in severe ureteric branching and stromal mesenchymal defects, although loss of Frs2α (major signaling adapter for Fgfrs) in the UB causes only mild renal hypoplasia. Deletion of both Fgfr1 and Fgfr2 in the MM results in renal aplasia with defects in MM formation and initial UB elongation and branching. Loss of Fgfr2 in the MM leads to many renal and urinary tract anomalies as well as vesicoureteral reflux. Thus, Fgfr signaling is critical for patterning of virtually all renal lineages at early and later stages of development.

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Expression and localization of fibroblast growth factors and fibroblast growth factor receptors in the developing rat kidney

Abstract: These results indicate that FGFs and FGFRs are expressed in the developing rat metanephros from at least E14 and that they likely play important roles in metanephric development and maturation.

Cited by 64 publications

References 47 publications

Transcript profiling of Wilms tumors reveals connections to kidney morphogenesis and expression patterns associated with anaplasia

Transcript profiling of Wilms tumors reveals connections to kidney morphogenesis and expression patterns associated with anaplasia

FGFR3IIIS: a novel soluble FGFR3 spliced variant that modulates growth is frequently expressed in tumour cells

Role of fibroblast growth factor receptor signaling in kidney development

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