Bmp7 Maintains Undifferentiated Kidney Progenitor Population and Determines Nephron Numbers at Birth
The number of nephrons, the functional units of the kidney, varies among individuals. A low nephron number at birth is associated with a risk of hypertension and the progression of renal insufficiency. The molecular mechanisms determining nephron number during embryogenesis have not yet been clarifi...
Autores principales: | , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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Public Library of Science
2013
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Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3753328/ https://www.ncbi.nlm.nih.gov/pubmed/23991197 http://dx.doi.org/10.1371/journal.pone.0073554 |
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author | Tomita, Mayumi Asada, Misako Asada, Nariaki Nakamura, Jin Oguchi, Akiko Higashi, Atsuko Y. Endo, Shuichiro Robertson, Elizabeth Kimura, Takeshi Kita, Toru Economides, Aris N. Kreidberg, Jordan Yanagita, Motoko |
author_facet | Tomita, Mayumi Asada, Misako Asada, Nariaki Nakamura, Jin Oguchi, Akiko Higashi, Atsuko Y. Endo, Shuichiro Robertson, Elizabeth Kimura, Takeshi Kita, Toru Economides, Aris N. Kreidberg, Jordan Yanagita, Motoko |
author_sort | Tomita, Mayumi |
collection | PubMed |
description | The number of nephrons, the functional units of the kidney, varies among individuals. A low nephron number at birth is associated with a risk of hypertension and the progression of renal insufficiency. The molecular mechanisms determining nephron number during embryogenesis have not yet been clarified. Germline knockout of bone morphogenetic protein 7 (Bmp7) results in massive apoptosis of the kidney progenitor cells and defects in early stages of nephrogenesis. This phenotype has precluded analysis of Bmp7 function in the later stage of nephrogenesis. In this study, utilization of conditional null allele of Bmp7 in combination with systemic inducible Cre deleter mice enabled us to analyze Bmp7 function at desired time points during kidney development, and to discover the novel function of Bmp7 to inhibit the precocious differentiation of the progenitor cells to nephron. Systemic knockout of Bmp7 in vivo after the initiation of kidney development results in the precocious differentiation of the kidney progenitor cells to nephron, in addition to the prominent apoptosis of progenitor cells. We also confirmed that in vitro knockout of Bmp7 in kidney explant culture results in the accelerated differentiation of progenitor population. Finally we utilized colony-forming assays and demonstrated that Bmp7 inhibits epithelialization and differentiation of the kidney progenitor cells. These results indicate that the function of Bmp7 to inhibit the precocious differentiation of the progenitor cells together with its anti-apoptotic effect on progenitor cells coordinately maintains renal progenitor pool in undifferentiated status, and determines the nephron number at birth. |
format | Online Article Text |
id | pubmed-3753328 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2013 |
publisher | Public Library of Science |
record_format | MEDLINE/PubMed |
spelling | pubmed-37533282013-08-29 Bmp7 Maintains Undifferentiated Kidney Progenitor Population and Determines Nephron Numbers at Birth Tomita, Mayumi Asada, Misako Asada, Nariaki Nakamura, Jin Oguchi, Akiko Higashi, Atsuko Y. Endo, Shuichiro Robertson, Elizabeth Kimura, Takeshi Kita, Toru Economides, Aris N. Kreidberg, Jordan Yanagita, Motoko PLoS One Research Article The number of nephrons, the functional units of the kidney, varies among individuals. A low nephron number at birth is associated with a risk of hypertension and the progression of renal insufficiency. The molecular mechanisms determining nephron number during embryogenesis have not yet been clarified. Germline knockout of bone morphogenetic protein 7 (Bmp7) results in massive apoptosis of the kidney progenitor cells and defects in early stages of nephrogenesis. This phenotype has precluded analysis of Bmp7 function in the later stage of nephrogenesis. In this study, utilization of conditional null allele of Bmp7 in combination with systemic inducible Cre deleter mice enabled us to analyze Bmp7 function at desired time points during kidney development, and to discover the novel function of Bmp7 to inhibit the precocious differentiation of the progenitor cells to nephron. Systemic knockout of Bmp7 in vivo after the initiation of kidney development results in the precocious differentiation of the kidney progenitor cells to nephron, in addition to the prominent apoptosis of progenitor cells. We also confirmed that in vitro knockout of Bmp7 in kidney explant culture results in the accelerated differentiation of progenitor population. Finally we utilized colony-forming assays and demonstrated that Bmp7 inhibits epithelialization and differentiation of the kidney progenitor cells. These results indicate that the function of Bmp7 to inhibit the precocious differentiation of the progenitor cells together with its anti-apoptotic effect on progenitor cells coordinately maintains renal progenitor pool in undifferentiated status, and determines the nephron number at birth. Public Library of Science 2013-08-26 /pmc/articles/PMC3753328/ /pubmed/23991197 http://dx.doi.org/10.1371/journal.pone.0073554 Text en © 2013 Tomita et al http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited. |
spellingShingle | Research Article Tomita, Mayumi Asada, Misako Asada, Nariaki Nakamura, Jin Oguchi, Akiko Higashi, Atsuko Y. Endo, Shuichiro Robertson, Elizabeth Kimura, Takeshi Kita, Toru Economides, Aris N. Kreidberg, Jordan Yanagita, Motoko Bmp7 Maintains Undifferentiated Kidney Progenitor Population and Determines Nephron Numbers at Birth |
title | Bmp7 Maintains Undifferentiated Kidney Progenitor Population and Determines Nephron Numbers at Birth |
title_full | Bmp7 Maintains Undifferentiated Kidney Progenitor Population and Determines Nephron Numbers at Birth |
title_fullStr | Bmp7 Maintains Undifferentiated Kidney Progenitor Population and Determines Nephron Numbers at Birth |
title_full_unstemmed | Bmp7 Maintains Undifferentiated Kidney Progenitor Population and Determines Nephron Numbers at Birth |
title_short | Bmp7 Maintains Undifferentiated Kidney Progenitor Population and Determines Nephron Numbers at Birth |
title_sort | bmp7 maintains undifferentiated kidney progenitor population and determines nephron numbers at birth |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3753328/ https://www.ncbi.nlm.nih.gov/pubmed/23991197 http://dx.doi.org/10.1371/journal.pone.0073554 |
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