Ablation of the renal stroma defines its critical role in nephron progenitor and vasculature patterning
The renal stroma is an embryonic cell population located in the cortex that provides a structural framework as well as a source of endothelial progenitors for the developing kidney. The exact role of the renal stroma in normal kidney development hasn't been clearly defined. However, previous st...
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| description | The renal stroma is an embryonic cell population located in the cortex that provides a structural framework as well as a source of endothelial progenitors for the developing kidney. The exact role of the renal stroma in normal kidney development hasn't been clearly defined. However, previous studies have shown that the genetic deletion of Foxd1, a renal stroma specific gene, leads to severe kidney malformations confirming the importance of stroma in normal kidney development. This study further investigates the role of renal stroma by ablating Foxd1-derived stroma cells themselves and observing the response of the remaining cell populations. A Foxd1cre (renal stroma specific) mouse was crossed with a diphtheria toxin mouse (DTA) to specifically induce apoptosis in stromal cells. Histological examination of kidneys at embryonic day 13.5-18.5 showed a lack of stromal tissue, mispatterning of renal structures, and dysplastic and/or fused horseshoe kidneys. Immunofluorescence staining of nephron progenitors, vasculature, ureteric epithelium, differentiated nephron progenitors, and vascular supportive cells revealed that mutants had thickened nephron progenitor caps, cortical regions devoid of nephron progenitors, aberrant vessel patterning and thickening, ureteric branching defects and migration of differentiated nephron structures into the medulla. The similarities between the renal deformities caused by Foxd1 genetic knockout and Foxd1DTA mouse models reveal the importance of Foxd1 in mediating and maintaining the functional integrity of the renal stroma. |
| doi_str_mv | 10.1371/journal.pone.0088400 |
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The exact role of the renal stroma in normal kidney development hasn't been clearly defined. However, previous studies have shown that the genetic deletion of Foxd1, a renal stroma specific gene, leads to severe kidney malformations confirming the importance of stroma in normal kidney development. This study further investigates the role of renal stroma by ablating Foxd1-derived stroma cells themselves and observing the response of the remaining cell populations. A Foxd1cre (renal stroma specific) mouse was crossed with a diphtheria toxin mouse (DTA) to specifically induce apoptosis in stromal cells. Histological examination of kidneys at embryonic day 13.5-18.5 showed a lack of stromal tissue, mispatterning of renal structures, and dysplastic and/or fused horseshoe kidneys. Immunofluorescence staining of nephron progenitors, vasculature, ureteric epithelium, differentiated nephron progenitors, and vascular supportive cells revealed that mutants had thickened nephron progenitor caps, cortical regions devoid of nephron progenitors, aberrant vessel patterning and thickening, ureteric branching defects and migration of differentiated nephron structures into the medulla. The similarities between the renal deformities caused by Foxd1 genetic knockout and Foxd1DTA mouse models reveal the importance of Foxd1 in mediating and maintaining the functional integrity of the renal stroma.</description><identifier>ISSN: 1932-6203</identifier><identifier>EISSN: 1932-6203</identifier><identifier>DOI: 10.1371/journal.pone.0088400</identifier><identifier>PMID: 24505489</identifier><language>eng</language><publisher>United States: Public Library of Science</publisher><subject>Aberration ; Ablation (Surgery) ; Analysis ; Animal models ; Animals ; Apoptosis ; Auditory defects ; Biology ; Body Patterning ; Cell Differentiation ; Cell division ; Children & youth ; Clonal deletion ; Deformation mechanisms ; Diphtheria ; Diphtheria toxin ; Embryos ; Epithelium ; Female ; Forkhead Transcription Factors - genetics ; Gene deletion ; Gene expression ; Immunofluorescence ; Kidney - abnormalities ; Kidney - blood supply ; Kidney - embryology ; Kidney - metabolism ; Kidneys ; Medicine ; Mice ; Morphogenesis ; Mutants ; Mutation ; Nephrology ; Nephrons - cytology ; Pattern formation ; Pediatrics ; Physicians ; Physiology ; Rodents ; Stem cells ; Stem Cells - cytology ; Stromal cells ; Thermal analysis ; Thickening ; Transcription factors ; Ureter</subject><ispartof>PloS one, 2014-02, Vol.9 (2), p.e88400-e88400</ispartof><rights>COPYRIGHT 2014 Public Library of Science</rights><rights>2014 Hum et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License: http://creativecommons.org/licenses/by/4.0/ (the “License”), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.</rights><rights>2014 Hum et al 2014 Hum et al</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c758t-5267037f7d7b746ce632eb2c0030e66d4e26002a58e9da05ec31cb72b8e40c143</citedby><cites>FETCH-LOGICAL-c758t-5267037f7d7b746ce632eb2c0030e66d4e26002a58e9da05ec31cb72b8e40c143</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC3914987/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC3914987/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,723,776,780,860,881,2096,2915,23845,27901,27902,53766,53768,79569,79570</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/24505489$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Hum, Stephanie</creatorcontrib><creatorcontrib>Rymer, Christopher</creatorcontrib><creatorcontrib>Schaefer, Caitlin</creatorcontrib><creatorcontrib>Bushnell, Daniel</creatorcontrib><creatorcontrib>Sims-Lucas, Sunder</creatorcontrib><title>Ablation of the renal stroma defines its critical role in nephron progenitor and vasculature patterning</title><title>PloS one</title><addtitle>PLoS One</addtitle><description>The renal stroma is an embryonic cell population located in the cortex that provides a structural framework as well as a source of endothelial progenitors for the developing kidney. The exact role of the renal stroma in normal kidney development hasn't been clearly defined. However, previous studies have shown that the genetic deletion of Foxd1, a renal stroma specific gene, leads to severe kidney malformations confirming the importance of stroma in normal kidney development. This study further investigates the role of renal stroma by ablating Foxd1-derived stroma cells themselves and observing the response of the remaining cell populations. A Foxd1cre (renal stroma specific) mouse was crossed with a diphtheria toxin mouse (DTA) to specifically induce apoptosis in stromal cells. Histological examination of kidneys at embryonic day 13.5-18.5 showed a lack of stromal tissue, mispatterning of renal structures, and dysplastic and/or fused horseshoe kidneys. Immunofluorescence staining of nephron progenitors, vasculature, ureteric epithelium, differentiated nephron progenitors, and vascular supportive cells revealed that mutants had thickened nephron progenitor caps, cortical regions devoid of nephron progenitors, aberrant vessel patterning and thickening, ureteric branching defects and migration of differentiated nephron structures into the medulla. The similarities between the renal deformities caused by Foxd1 genetic knockout and Foxd1DTA mouse models reveal the importance of Foxd1 in mediating and maintaining the functional integrity of the renal stroma.</description><subject>Aberration</subject><subject>Ablation (Surgery)</subject><subject>Analysis</subject><subject>Animal models</subject><subject>Animals</subject><subject>Apoptosis</subject><subject>Auditory defects</subject><subject>Biology</subject><subject>Body Patterning</subject><subject>Cell Differentiation</subject><subject>Cell division</subject><subject>Children & youth</subject><subject>Clonal deletion</subject><subject>Deformation mechanisms</subject><subject>Diphtheria</subject><subject>Diphtheria toxin</subject><subject>Embryos</subject><subject>Epithelium</subject><subject>Female</subject><subject>Forkhead Transcription Factors - genetics</subject><subject>Gene deletion</subject><subject>Gene expression</subject><subject>Immunofluorescence</subject><subject>Kidney - abnormalities</subject><subject>Kidney - blood supply</subject><subject>Kidney - embryology</subject><subject>Kidney - metabolism</subject><subject>Kidneys</subject><subject>Medicine</subject><subject>Mice</subject><subject>Morphogenesis</subject><subject>Mutants</subject><subject>Mutation</subject><subject>Nephrology</subject><subject>Nephrons - cytology</subject><subject>Pattern formation</subject><subject>Pediatrics</subject><subject>Physicians</subject><subject>Physiology</subject><subject>Rodents</subject><subject>Stem cells</subject><subject>Stem Cells - cytology</subject><subject>Stromal cells</subject><subject>Thermal analysis</subject><subject>Thickening</subject><subject>Transcription factors</subject><subject>Ureter</subject><issn>1932-6203</issn><issn>1932-6203</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2014</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>BENPR</sourceid><sourceid>DOA</sourceid><recordid>eNqNk12L1DAUhoso7jr6D0QLgujFjGmS5uNGGBY_BhYW_LoNaXraydJJxiRd9N-bcbrLVPZCcpGQPO97ck5yiuJ5hVYV4dW7az8Gp4fV3jtYISQERehBcV5JgpcMI_LwZH1WPInxGqGaCMYeF2eY1qimQp4X_boZdLLelb4r0xbKANm0jCn4nS5b6KyDWNoUSxNssiafBT9AaV3pYL8NWbgPvgdnkw-ldm15o6MZs-cYoNzrlCA46_qnxaNODxGeTfOi-P7xw7eLz8vLq0-bi_Xl0vBapGWNGUeEd7zlDafMACMYGmwQIggYaylghhDWtQDZalSDIZVpOG4EUGQqShbFy6PvfvBRTTWKqpKCUEwoZZnYHInW62u1D3anw2_ltVV_N3zolQ450wEUZVBzIjghRlKJQWpDSYMkExoRU5Hs9X6KNjY7aA24FPQwM52fOLtVvb9RRFZUZuNF8WYyCP7nCDGpnY0GhkE78GO-N5WyIqiWh1iv_kHvz26iep0TsK7zOa45mKo15UJgzrnM1OoeKo8WdtbkD9XZvD8TvJ0JMpPgV-r1GKPafP3y_-zVjzn7-oTdgh7SNvphPPzIOAfpETTBxxiguytyhdShH26roQ79oKZ-yLIXpw90J7ptAPIHnwwFZw</recordid><startdate>20140205</startdate><enddate>20140205</enddate><creator>Hum, Stephanie</creator><creator>Rymer, Christopher</creator><creator>Schaefer, Caitlin</creator><creator>Bushnell, Daniel</creator><creator>Sims-Lucas, Sunder</creator><general>Public Library of Science</general><general>Public Library of Science (PLoS)</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>IOV</scope><scope>ISR</scope><scope>3V.</scope><scope>7QG</scope><scope>7QL</scope><scope>7QO</scope><scope>7RV</scope><scope>7SN</scope><scope>7SS</scope><scope>7T5</scope><scope>7TG</scope><scope>7TM</scope><scope>7U9</scope><scope>7X2</scope><scope>7X7</scope><scope>7XB</scope><scope>88E</scope><scope>8AO</scope><scope>8C1</scope><scope>8FD</scope><scope>8FE</scope><scope>8FG</scope><scope>8FH</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABJCF</scope><scope>ABUWG</scope><scope>AEUYN</scope><scope>AFKRA</scope><scope>ARAPS</scope><scope>ATCPS</scope><scope>AZQEC</scope><scope>BBNVY</scope><scope>BENPR</scope><scope>BGLVJ</scope><scope>BHPHI</scope><scope>C1K</scope><scope>CCPQU</scope><scope>D1I</scope><scope>DWQXO</scope><scope>FR3</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>GNUQQ</scope><scope>H94</scope><scope>HCIFZ</scope><scope>K9.</scope><scope>KB.</scope><scope>KB0</scope><scope>KL.</scope><scope>L6V</scope><scope>LK8</scope><scope>M0K</scope><scope>M0S</scope><scope>M1P</scope><scope>M7N</scope><scope>M7P</scope><scope>M7S</scope><scope>NAPCQ</scope><scope>P5Z</scope><scope>P62</scope><scope>P64</scope><scope>PATMY</scope><scope>PDBOC</scope><scope>PHGZM</scope><scope>PHGZT</scope><scope>PIMPY</scope><scope>PJZUB</scope><scope>PKEHL</scope><scope>PPXIY</scope><scope>PQEST</scope><scope>PQGLB</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PRINS</scope><scope>PTHSS</scope><scope>PYCSY</scope><scope>RC3</scope><scope>7X8</scope><scope>5PM</scope><scope>DOA</scope></search><sort><creationdate>20140205</creationdate><title>Ablation of the renal stroma defines its critical role in nephron progenitor and vasculature patterning</title><author>Hum, Stephanie ; Rymer, Christopher ; Schaefer, Caitlin ; Bushnell, Daniel ; Sims-Lucas, Sunder</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c758t-5267037f7d7b746ce632eb2c0030e66d4e26002a58e9da05ec31cb72b8e40c143</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2014</creationdate><topic>Aberration</topic><topic>Ablation (Surgery)</topic><topic>Analysis</topic><topic>Animal models</topic><topic>Animals</topic><topic>Apoptosis</topic><topic>Auditory defects</topic><topic>Biology</topic><topic>Body Patterning</topic><topic>Cell Differentiation</topic><topic>Cell division</topic><topic>Children & youth</topic><topic>Clonal deletion</topic><topic>Deformation mechanisms</topic><topic>Diphtheria</topic><topic>Diphtheria toxin</topic><topic>Embryos</topic><topic>Epithelium</topic><topic>Female</topic><topic>Forkhead Transcription Factors - 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Academic</collection><collection>PubMed Central (Full Participant titles)</collection><collection>DOAJ Directory of Open Access Journals</collection><jtitle>PloS one</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Hum, Stephanie</au><au>Rymer, Christopher</au><au>Schaefer, Caitlin</au><au>Bushnell, Daniel</au><au>Sims-Lucas, Sunder</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Ablation of the renal stroma defines its critical role in nephron progenitor and vasculature patterning</atitle><jtitle>PloS one</jtitle><addtitle>PLoS One</addtitle><date>2014-02-05</date><risdate>2014</risdate><volume>9</volume><issue>2</issue><spage>e88400</spage><epage>e88400</epage><pages>e88400-e88400</pages><issn>1932-6203</issn><eissn>1932-6203</eissn><abstract>The renal stroma is an embryonic cell population located in the cortex that provides a structural framework as well as a source of endothelial progenitors for the developing kidney. The exact role of the renal stroma in normal kidney development hasn't been clearly defined. However, previous studies have shown that the genetic deletion of Foxd1, a renal stroma specific gene, leads to severe kidney malformations confirming the importance of stroma in normal kidney development. This study further investigates the role of renal stroma by ablating Foxd1-derived stroma cells themselves and observing the response of the remaining cell populations. A Foxd1cre (renal stroma specific) mouse was crossed with a diphtheria toxin mouse (DTA) to specifically induce apoptosis in stromal cells. Histological examination of kidneys at embryonic day 13.5-18.5 showed a lack of stromal tissue, mispatterning of renal structures, and dysplastic and/or fused horseshoe kidneys. Immunofluorescence staining of nephron progenitors, vasculature, ureteric epithelium, differentiated nephron progenitors, and vascular supportive cells revealed that mutants had thickened nephron progenitor caps, cortical regions devoid of nephron progenitors, aberrant vessel patterning and thickening, ureteric branching defects and migration of differentiated nephron structures into the medulla. The similarities between the renal deformities caused by Foxd1 genetic knockout and Foxd1DTA mouse models reveal the importance of Foxd1 in mediating and maintaining the functional integrity of the renal stroma.</abstract><cop>United States</cop><pub>Public Library of Science</pub><pmid>24505489</pmid><doi>10.1371/journal.pone.0088400</doi><oa>free_for_read</oa></addata></record> |
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| subjects | Aberration Ablation (Surgery) Analysis Animal models Animals Apoptosis Auditory defects Biology Body Patterning Cell Differentiation Cell division Children & youth Clonal deletion Deformation mechanisms Diphtheria Diphtheria toxin Embryos Epithelium Female Forkhead Transcription Factors - genetics Gene deletion Gene expression Immunofluorescence Kidney - abnormalities Kidney - blood supply Kidney - embryology Kidney - metabolism Kidneys Medicine Mice Morphogenesis Mutants Mutation Nephrology Nephrons - cytology Pattern formation Pediatrics Physicians Physiology Rodents Stem cells Stem Cells - cytology Stromal cells Thermal analysis Thickening Transcription factors Ureter |
| title | Ablation of the renal stroma defines its critical role in nephron progenitor and vasculature patterning |
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