Renal and neuronal abnormalities in mice lacking GDNF

Moore, Mark; Klein, Robert D.; Fariñas, Isabel; Sauer, H.; Armanini, Mark; Phillips, Heidi S.; Reichardt, Louis F.; Ryan, Anne; Carver-Moore, Karen; Rosenthal, Arnon

doi:10.1038/382076a0

Cited by 1,161 publications

(776 citation statements)

References 28 publications

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“…GDNF is the ligand for the Ret receptor tyrosine kinase, which is expressed in the ureteric bud tips. Both Gdnf and Ret are required for normal branching of the UB [54,55]. When Ret +/− mice are crossed with Wnt11 +/− mice, the resulting kidneys of the double heterozygotes are 52% smaller than those of wildtype.…”

Section: The Role Of Wnt Signaling In Branching Morphogenesismentioning

confidence: 99%

Molecular regulation of kidney development: is the answer blowing in the Wnt?

2007

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Development of the metanephric kidney is a complicated process regulated by reciprocal signals from the ureteric bud and the metanephric mesenchyme that regulate tubule formation and epithelial branching morphogenesis. Over the past several years, several studies have suggested that Wnt signaling is involved in multiple aspects of normal kidney development as well as injury response and cancer progression. We will review these data here.

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Section: The Role Of Wnt Signaling In Branching Morphogenesismentioning

confidence: 99%

Molecular regulation of kidney development: is the answer blowing in the Wnt?

2007

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“…In situ hybridization studies have localized RET expression to the ureteric bud in embryonic murine kidney (Pachnis et al, 1993). Consistent with RET involvement in the induction of kidney morphogenesis, the RET knockout (7/7) mouse has kidney agenesis or severe dysgenesis (Schuchardt et al, 1994(Schuchardt et al, , 1996 as do mice lacking glial cell line-derived neurotrophic factor (GDNF) which encodes the soluble portion of the RET ligand (Moore et al, 1996;Pichel et al, 1996;SaÂ nchez et al, 1996). RET's proposed role as a transducer of mesenchymederived signals in kidney induction is supported by the localization of GDNF expression to the metanephric mesenchyme with highest expression in early developmental stages (Durbec et al, 1996a;Hellmich et al, 1996;Trupp et al, 1996).…”

Section: Introductionmentioning

confidence: 98%

Expression of RET 3′ splicing variants during human kidney development

1998

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The mature mammalian kidney arises through a series of reciprocal inductive interactions between two di erent cell groups, the ureteric bud epithelium and the metanephric mesenchyme. The RET receptor tyrosine kinase is required for induction and development of the metanephric kidney. Di erential splicing at the 3' end of RET results in transcripts encoding three isoforms that di er with respect to their C-terminal 9 (RET9), 51 (RET51) or 43 (RET43) amino acids. In vitro assays have identi®ed di erences in the abilities of the RET9 and RET51 isoforms to induce di erentiation suggesting functional di erences between these proteins. We examined the relative expression levels of the three RET 3' splicing variants in developing human kidney using semi-quantitative RT ± PCR. We observed consistent expression of the RET9 and RET43 variants in kidney samples spanning 7.5 through 24 weeks gestation. At early gestational ages (7.5 ± 8.5 weeks), RET51 expression was very low (+5%) compared to RET9; however, a rapid seven fold increase in expression was detected by 9 weeks. Our data suggest that RET51 may contribute to di erentiation-related events occurring after 8.5 weeks gestation rather than to induction of the human kidney.

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“…(27) The key role of GDNF and its receptors in kidney development was initially revealed by the targeted disruption of the Ret, GDNF and Gfra1 genes. (28)(29)(30)(31)(32)(33) Mice lacking any one of these genes had similar excretory system defects, ranging from renal agenesis, to blind ending ureters with no renal tissue, to tiny, disorganized kidney rudiments. These findings established that the GDNF signal is important to induce the outgrowth of the UB from the WD and to promote its early growth and branching.…”

Section: Introductionmentioning

confidence: 99%

GDNF/Ret signaling and the development of the kidney

2006

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SummarySignaling by GDNF through the Ret receptor is required for normal growth of the ureteric bud during kidney development. However, the precise role of GDNF/Ret signaling in renal branching morphogenesis and the specific responses of ureteric bud cells to GDNF remain unclear. Recent studies have provided new insight into these issues. The localized expression of GDNF by the metanephric mesenchyme, together with several types of negative regulation, is important to elicit and correctly position the initial budding event from the Wolffian duct. GDNF also promotes the continued branching of the ureteric bud. However, it does not provide the positional information required to specify the pattern of ureteric bud growth and branching, as its site of synthesis can be drastically altered with minimal effects on kidney development. Cells that lack Ret are unable to contribute to the tip of the ureteric bud, apparently because GDNF-driven proliferation is required for the formation and growth of this specialized epithelial domain.

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Renal and neuronal abnormalities in mice lacking GDNF

Cited by 1,161 publications

References 28 publications

Molecular regulation of kidney development: is the answer blowing in the Wnt?

Molecular regulation of kidney development: is the answer blowing in the Wnt?

Expression of RET 3′ splicing variants during human kidney development

GDNF/Ret signaling and the development of the kidney

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