Journal
DEVELOPMENTAL BIOLOGY
Volume 310, Issue 2, Pages 379-387Publisher
ACADEMIC PRESS INC ELSEVIER SCIENCE
DOI: 10.1016/j.ydbio.2007.08.021
Keywords
kidney; renal organogenesis; renal morphogenesis; nephrogenesis; confocal microscopy; postnatal development; mouse; apoptosis; proliferation
Categories
Funding
- NIDDK NIH HHS [K08 DK002702-04, K08 DK002702, DK02702, R01 DK061916-06, R01 DK061916, DK61916] Funding Source: Medline
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The kidney develops by cycles of ureteric bud branching and nephron formation. The cycles begin and are sustained by reciprocal inductive interactions and feedback between ureteric bud tips and the surrounding mesenchyme. Understanding how the cycles end is important because it controls nephron number. During the period when nephrogenesis ends in mice, we examined the morphology, gene expression, and function of the domains that control branching and nephrogenesis. We found that the nephrogenic mesenchyme, which is required for continued branching, was gone by the third postnatal day. This was associated with an accelerated rate of new nephron formation in the absence of apoptosis. At the same time, the tips of the ureteric bud branches lost the typical appearance of an ampulla and lost Wnt11 expression, consistent with the absence of the capping mesenchyme. Surprisingly, expression of Wnt9b, a gene necessary for mesenchyme induction, continued. We then tested the postnatal day three bud branch tip and showed that it maintained its ability both to promote survival of metanephric mesenchyme and to induce nephrogenesis in culture. These results suggest that the sequence of events leading to disruption of the cycle of branching morphogenesis and nephrogenesis began with the loss of mesenchyme that resulted from its conversion into nephrons. (C) 2007 Elsevier Inc. All rights reserved.
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