Distal ureter morphogenesis depends on epithelial cell remodeling mediated by vitamin A and Ret

Batourina, Ekatherina; Choi, Christopher; Paragas, Neal; Bello, Natalie A.; Hensle, Terry W.; Costantini, Frank; Schuchardt, Anita; Bacallao, Robert L.; Mendelsohn, Cathy

doi:10.1038/ng952

Cited by 147 publications

(130 citation statements)

References 35 publications

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“…In situ hybridization was performed as previously described in developing (embryonic day 15.5) and adult kidneys by using digoxigenin-labeled riboprobes (19). cDNA encoding a fragment from mouse Prmt7 (GenBank entry no.…”

Section: Measurement Of Gene Expression By Real-time Pcrmentioning

confidence: 99%

A Mendelian locus on chromosome 16 determines susceptibility to doxorubicin nephropathy in the mouse

Zheng

Schmidt‐Ott

Chua

et al. 2005

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

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The development of kidney disease is influenced by both genetic and environmental factors. Searching for models of glomerulopathy that display strong gene-environment interaction, we examined the determinants of anthracycline-induced nephropathy, a classic, strain-dependent experimental model applied to rodents in the past four decades. We produced three crosses derived from mice with contrasting susceptibility to doxorubicin (DOX) nephropathy and, surprisingly, we found that this widely studied model segregates as a single-gene defect with recessive inheritance. By genome-wide analysis of linkage, we mapped the trait locus to chromosome 16A1-B1 (DOXNPH locus) in all three crosses [peak logarithm of odds (lod) score of 92.7, P ‫؍‬ 1 ؋ 10 ؊65 ]; this interval represents a susceptibility locus for nephropathy. Gene expression analysis indicated that susceptibility alleles at the DOXNPH locus are associated with blunted expression of protein arginine methyltransferase 7 (Prmt7) on chromosome 8, a protein previously implicated in cellular sensitivity to chemotherapeutic agents (lod ‫؍‬ 12.4, P ‫؍‬ 0.0001). Therefore, Prmt7 expression serves as a molecular marker for susceptibility to DOX nephropathy. Finally, increased variation in the severity of kidney disease among affected mice motivated a second genome-wide search, identifying a locus on chromosome 9 that influences the severity and progression of nephropathy (DOXmod, peak lod score 4.3, P ‫؍‬ 0.0018). These data provide genetic and molecular characterization of a previously unrecognized Mendelian trait. Elucidation of DOX nephropathy may simultaneously provide insight into the pathogenesis of renal failure and mechanisms of cytotoxicity induced by chemotherapeutic agents.genetics

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Section: Measurement Of Gene Expression By Real-time Pcrmentioning

confidence: 99%

A Mendelian locus on chromosome 16 determines susceptibility to doxorubicin nephropathy in the mouse

Zheng

Schmidt‐Ott

Chua

et al. 2005

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

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“…The phenotypes of gene knockout mice have revealed that several growth and signaling factor families play fundamental roles in reproductive and urogenital organ formation (Batourina et al, 2002;Doles et al, 2006;Haraguchi et al, 2001;Haraguchi et al, 2000;Huang et al, 2005;Jamin et al, 2002;Kobayashi and Behringer, 2003;Kondo et al, 1996;McMahon et al, 2003;Morgan et al, 2003;Perriton et al, 2002;Suzuki et al, 2003). Shh is expressed in the cloacal epithelia and is vital for the regulation of structures derived from the genital tubercle (GT) and the urogenital sinus, such as the external genitalia and the prostate, respectively (de Santa Barbara and Roberts, 2002;Freestone et al, 2003;Pu et al, 2004).…”

Section: Introductionmentioning

confidence: 99%

Molecular analysis of coordinated bladder and urogenital organ formation by Hedgehog signaling

Haraguchi

Motoyama

Sasaki³

et al. 2007

Development

137

162

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The urogenital and reproductive organs, including the external genitalia, bladder and urethra, develop as anatomically aligned organs. Descriptive and experimental embryology suggest that the cloaca, and its derivative, the urogenital sinus, contribute to the formation of these organs. However, it is unknown how the primary tissue lineages in, and adjacent to, the cloaca give rise to the above organs, nor is bladder formation understood. While it is known that sonic hedgehog (Shh) is expressed by the cloacal epithelia, the developmental programs that regulate and coordinate the formation of the urogenital and reproductive organs have not been elucidated. Here we report that Shh mutant embryos display hypoplasia of external genitalia, internal urethra (pelvic urethra) and bladder. The importance of Shh signaling in the development of bladder and external genitalia was confirmed by analyzing a variety of mutant mouse lines with defective hedgehog signaling. By genetically labeling hedgehog-responding tissue lineages adjacent to the cloaca and urogenital sinus, we defined the contribution of these tissues to the bladder and external genitalia. We discovered that development of smooth muscle myosin-positive embryonic bladder mesenchyme requires Shh signaling, and that the bladder mesenchyme and dorsal (upper) external genitalia derive from Shh-responsive peri-cloacal mesenchyme. Thus, the mesenchymal precursors for multiple urogenital structures derive from peri-cloacal mesenchyme and the coordination of urogenital organ formation from these precursors is orchestrated by Shh signals.

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“…43,44 the part of the mesonephric duct between newly developed ureter and urogenital sinus is subsequently removed by apoptosis, 45 whereupon the free end of the developing ureter inserts into the bladder wall and the vesicoureteric valve is formed. 41,46,47 the mechanism of vur and subsequent reflux nephro pathy is based on the disruption of a proper valvular mechanism at the vesicoureteric junction, which leads to retrograde flow of urine into the ureter or kidney. this disruption is most likely the result of a shortened intravesical ureter, and an enlarged or malpositioned ureteric orifice.…”

Section: Vur Is a Complex Diseasementioning

confidence: 99%

Genetics of vesicoureteral reflux

et al. 2011

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| Primary vesicoureteral reflux (VUR) is the most common urological anomaly in children, affecting 1-2% of the pediatric population and 30-40% of children presenting with urinary tract infections (UTIs). Refluxassociated nephropathy is a major cause of childhood hypertension and chronic renal failure. The hereditary and familial nature of VUR is well recognized and several studies have reported that siblings of children with VUR have a higher incidence of reflux than the general pediatric population. Familial clustering of VUR implies that genetic factors have an important role in its pathogenesis, but no single major locus or gene for VUR has yet been identified and most researchers now acknowledge that VUR is genetically heterogeneous. Improvements in genome-scan techniques and continuously increasing knowledge of the genetic basis of VUR should help us to further understand its pathogenesis.

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Distal ureter morphogenesis depends on epithelial cell remodeling mediated by vitamin A and Ret

Cited by 147 publications

References 35 publications

A Mendelian locus on chromosome 16 determines susceptibility to doxorubicin nephropathy in the mouse

A Mendelian locus on chromosome 16 determines susceptibility to doxorubicin nephropathy in the mouse

Molecular analysis of coordinated bladder and urogenital organ formation by Hedgehog signaling

Genetics of vesicoureteral reflux

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