Postnatal prolongation of mammalian nephrogenesis by excess fetal GDNF

Hao Li, Kristen Kurtzeborn, Jussi Kupari, Yujuan Gui, Edward Siefker, Benson Lu, Kärt Mätlik, Soophie Olfat, Ana R. Montaño-Rodríguez, Sung Ho Huh, Franklin Costantini, Jaan Olle Andressoo, Satu Kuure

Research output: Contribution to journalArticlepeer-review

10 Scopus citations


Nephron endowment, defined during the fetal period, dictates renal and related cardiovascular health throughout life. We show here that, despite its negative effects on kidney growth, genetic increase ofGDNF prolongs the nephrogenic program beyond its normal cessation. Multistage mechanistic analysis revealed that excess GDNF maintains nephron progenitors and nephrogenesis through increased expression of its secreted targets and augmented WNT signaling, leading to a two-part effect on nephron progenitor maintenance. Abnormally high GDNF in embryonic kidneys upregulates its known targets but also Wnt9b and Axin2, with concomitant deceleration of nephron progenitor proliferation. Decline of GDNF levels in postnatal kidneys normalizes the ureteric bud and creates a permissive environment for continuation of the nephrogenic program, as demonstrated by morphologically and molecularly normal postnatal nephron progenitor self-renewal and differentiation. These results establish that excess GDNF has a bi-phasic effect on nephron progenitors in mice, which can faithfully respond to GDNF dosage manipulation during the fetal and postnatal period. Our results suggest that sensing the signaling activity level is an important mechanism through which GDNF and other molecules contribute to nephron progenitor lifespan specification.

Original languageEnglish (US)
Article numberdev197475
JournalDevelopment (Cambridge)
Issue number10
StatePublished - May 2021


  • Differentiation
  • Kidney
  • Mouse
  • Nephrogenesis
  • Nephron progenitors

ASJC Scopus subject areas

  • Molecular Biology
  • Developmental Biology


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