GDNF induces branching and increased cell proliferation in the ureter of the mouse.
The secreted signaling molecule GDNF is expressed in the metanephric mesenchyme and has recently been implicated as a factor necessary for development of the metanephric kidney. We have examined the effects of GDNF on mouse kidney explants. We show that GDNF increases cell proliferation in ureter tips. There is an increase in the number of ureter tips and expansion and fusion of adjacent tips and some tips appear to grow toward the source of GDNF. These events are accompanied by transcriptional upregulation of several genes localized to the tips, including its own receptor, c-ret, the transcription factor Sox9, and the signal Wnt-11. These results support a model in which GDNF supplied by the mesenchyme regulates growth and branching in the metanephric kidney through the local regulation of ureter tip-specific factors.
Pepicelli
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CV
Biolabs, Harvard University, 16 Divinity Avenue, Cambridge, Massachusetts 02138, USA.
Kispert
A
A
Rowitch
D H
DH
McMahon
A P
AP
D000818:Animals; D002455:Cell Division / Q000187:drug effects; D005260:Female; D018507:Gene Expression Regulation, Developmental; D051100:Glial Cell Line-Derived Neurotrophic Factor; D006023:Glycoproteins / Q000096:biosynthesis / Q000235:genetics; D007763:Lac Operon; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008808:Mice, Inbred CBA; D008822:Mice, Transgenic; D008954:Models, Biological; D009414:Nerve Growth Factors / Q000494:pharmacology*; D009419:Nerve Tissue Proteins / Q000494:pharmacology*; D009924:Organ Culture Techniques; D015854:Up-Regulation; D014513:Ureter / Q000166:cytology / Q000187:drug effects* / Q000196:embryology*; D051153:Wnt Proteins
C495040:Gdnf protein, mouse; D051100:Glial Cell Line-Derived Neurotrophic Factor; D006023:Glycoproteins; D009414:Nerve Growth Factors; D009419:Nerve Tissue Proteins; D051153:Wnt Proteins