Postnatal prolongation of mammalian nephrogenesis by excess fetal GDNF

ABSTRACT 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 of GDNF prolongs nephrogenic program beyond normal cessation. Multi-stage mechanistic analysis revealed that excess maintains nephron progenitors nephrogenesis through increased expression secreted targets augmented WNT signaling, leading to a two-part effect progenitor maintenance. Abnormally high in embryonic kidneys upregulates known but also Wnt9b Axin2, with concomitant deceleration proliferation. Decline levels postnatal normalizes ureteric bud creates permissive environment for continuation program, as demonstrated by morphologically molecularly self-renewal differentiation. These results establish has bi-phasic mice, which can faithfully respond dosage manipulation period. Our suggest sensing signaling activity level is an important mechanism other molecules contribute lifespan specification.