Glial cell line-derived neurotrophic factor activates the receptor tyrosine kinase RET and promotes kidney morphogenesis.

Vega, Quinn; Worby, Carolyn A.; Lechner, Mark S.; Dixon, Jack E.; Dressler, Gregory R.

doi:10.1073/pnas.93.20.10657

Cited by 218 publications

(117 citation statements)

References 38 publications

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“…The application of GDNF-soaked beads adjacent to the Wolffian duct in organ culture, (21,42) or the transgenic misexpression of GDNF throughout the Wolffian duct in vivo, (43) causes multiple, ectopic ureteric buds to emerge (Fig. 2g-i).…”

Section: The Role Of Localized Gdnf/ret Signaling In Ureter Formationmentioning

confidence: 99%

“…(10) Addition of GDNF to kidney cultures can increase the number of UB tips, which suggested a stimulation of branching. (42,62) Conversely, GDNF antibodies (42,63) or a Ret-Ig fusion protein (64) inhibit growth of the kidney in vitro. Finally, GDNF is continuously required (but is not sufficient) for the branching of isolated UBs grown in Matrigel with conditioned medium from a mesenchymal cell line.…”

Section: The Role Of Localized Gdnf/ret Signaling In Ureter Formationmentioning

confidence: 99%

“…Once a tip domain has been established, these cells continue to proliferate under the influence of GDNF, giving rise to the ampulla, and then to the new tips that form by branching of the ampulla. The ability of GDNF to increase the rate of UB branching (42,62) may be a consequence of its role in the proliferation of tip cells; since formation of the ampulla is a prerequisite for branching, increasing the growth rate of the ampulla may increase the rate of formation of new branches.…”

Section: The Role Of Localized Gdnf/ret Signaling In Ureter Formationmentioning

confidence: 99%

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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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Section: The Role Of Localized Gdnf/ret Signaling In Ureter Formationmentioning

confidence: 99%

Section: The Role Of Localized Gdnf/ret Signaling In Ureter Formationmentioning

confidence: 99%

Section: The Role Of Localized Gdnf/ret Signaling In Ureter Formationmentioning

confidence: 99%

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GDNF/Ret signaling and the development of the kidney

2006

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“…Gdnf has been shown to act as a mesenchymal signal regulating ureteric bud outgrowth through its receptors c-Ret and Gfrα1 expressed in the ureteric epithelium (Vega et al, 1996;Sainio et al, 1997). The null embryos of Gdnf lack induction of the ureteric bud, resulting in the complete absence of the metanephric kidney, and Gdnf-soaked beads can ectopically induce budding of the ureter from the Wolffian duct (Pichel et al, 1996;Sainio et al, 1997).…”

Section: Six1 Is Also Required For the Expression Of Sall1 In The Metmentioning

confidence: 99%

Six1is required for the early organogenesis of mammalian kidney

et al. 2003

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The murine Six gene family, homologous to Drosophila sine oculis(so) which encodes a homeodomain transcription factor, is composed of six members (Six1-6). Among the six members, only the Six2gene has been previously shown to be expressed early in kidney development,but its function is unknown. We have recently found that the Six1gene is also expressed in the kidney. In the developing kidney, Six1is expressed in the uninduced metanephric mesenchyme at E10.5 and in the induced mesenchyme around the ureteric bud at E11.5. At E17.5 to P0, Six1 expression became restricted to a subpopulation of collecting tubule epithelial cells. To study its in vivo function, we have recently generated Six1 mutant mice. Loss of Six1 leads to a failure of ureteric bud invasion into the mesenchyme and subsequent apoptosis of the mesenchyme. These results indicate that Six1 plays an essential role in early kidney development. In Six1-/- kidney development, we have found that Pax2, Six2 and Sall1expression was markedly reduced in the metanephric mesenchyme at E10.5,indicating that Six1 is required for the expression of these genes in the metanephric mesenchyme. In contrast, Eya1 expression was unaffected in Six1-/- metanephric mesenchyme at E10.5,indicating that Eya1 may function upstream of Six1. Moreover, our results show that both Eya1 and Six1expression in the metanephric mesenchyme is preserved in Pax2-/- embryos at E10.5, further indicating that Pax2 functions downstream of Eya1 and Six1 in the metanephric mesenchyme. Thus, the epistatic relationship between Pax, Eya and Six genes in the metanephric mesenchyme during early kidney development is distinct from a genetic pathway elucidated in the Drosophila eye imaginal disc. Finally, our results show that Eya1 and Six1genetically interact during mammalian kidney development, because most compound heterozygous embryos show hypoplastic kidneys. These analyses establish a role for Six1 in the initial inductive step for metanephric development.

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“…GDNF is related to neural development (He et al, 2007 andGarces et al, 2000) and renal morphogenesis (He et al, 2007 andVega et al, 1996). In spermatogonial cells, this factor plays an important role in the regulation of proliferation and differentiation or undifferentiated (He et al, 2007, Naughton et al, 2006Takakoro et al, 2002;Meng et al, 2000 andHofmann et al, 2005).…”

Section: Ssc Markers and Differences Among Speciesmentioning

confidence: 99%