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Dicer function is required in the metanephric mesenchyme for early kidney development

Identifieur interne : 003388 ( Main/Exploration ); précédent : 003387; suivant : 003389

Dicer function is required in the metanephric mesenchyme for early kidney development

Auteurs : Jessica Y. S. Chu [États-Unis] ; Sunder Sims-Lucas [États-Unis] ; Daniel S. Bushnell [États-Unis] ; Andrew J. Bodnar [États-Unis] ; Jordan A. Kreidberg [États-Unis] ; Jacqueline Ho [États-Unis]

Source :

RBID : PMC:3962603

Descripteurs français

English descriptors

Abstract

MicroRNAs (miRNAs) are small, noncoding regulatory RNAs that act as posttranscriptional repressors by binding to the 3′-untranslated region (3′-UTR) of target genes. They require processing by Dicer, an RNase III enzyme, to become mature regulatory RNAs. Previous work from our laboratory revealed critical roles for miRNAs in nephron progenitors at midgestation (Ho J, Pandey P, Schatton T, Sims-Lucas S, Khalid M, Frank MH, Hartwig S, Kreidberg JA. J Am Soc Nephrol 22: 1053–1063, 2011). To interrogate roles for miRNAs in the early metanephric mesenchyme, which gives rise to nephron progenitors as well as the renal stroma during kidney development, we conditionally ablated Dicer function in this lineage. Despite normal ureteric bud outgrowth and condensation of the metanephric mesenchyme to form nephron progenitors, early loss of miRNAs in the metanephric mesenchyme resulted in severe renal dysgenesis. Nephron progenitors are initially correctly specified in the mutant kidneys, with normal expression of several transcription factors known to be critical in progenitors, including Six2, Pax2, Sall1, and Wt1. However, there is premature loss of the nephron progenitor marker Cited1, marked apoptosis, and increased expression of the proapoptotic protein Bim shortly after the initial inductive events in early kidney development. Subsequently, there is a failure in ureteric bud branching and nephron progenitor differentiation. Taken together, our data demonstrate a previously undetermined requirement for miRNAs during early kidney organogenesis and indicate a crucial role for miRNAs in regulating the survival of this lineage.


Url:
DOI: 10.1152/ajprenal.00426.2013
PubMed: 24500693
PubMed Central: 3962603


Affiliations:


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<term>Bcl-2-Like Protein 11</term>
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<term>Nephrons (enzymology)</term>
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<term>DEAD-box RNA helicases (génétique)</term>
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<term>Néphrons (malformations)</term>
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<term>DEAD-box RNA Helicases</term>
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<term>MicroRNAs</term>
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<term>Apoptose</term>
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<term>Protéine-11 analogue à Bcl-2</term>
<term>Régulation de l'expression des gènes au cours du développement</term>
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<div type="abstract" xml:lang="en">
<p>MicroRNAs (miRNAs) are small, noncoding regulatory RNAs that act as posttranscriptional repressors by binding to the 3′-untranslated region (3′-UTR) of target genes. They require processing by Dicer, an RNase III enzyme, to become mature regulatory RNAs. Previous work from our laboratory revealed critical roles for miRNAs in nephron progenitors at midgestation (Ho J, Pandey P, Schatton T, Sims-Lucas S, Khalid M, Frank MH, Hartwig S, Kreidberg JA.
<italic>J Am Soc Nephrol</italic>
22: 1053–1063, 2011). To interrogate roles for miRNAs in the early metanephric mesenchyme, which gives rise to nephron progenitors as well as the renal stroma during kidney development, we conditionally ablated Dicer function in this lineage. Despite normal ureteric bud outgrowth and condensation of the metanephric mesenchyme to form nephron progenitors, early loss of miRNAs in the metanephric mesenchyme resulted in severe renal dysgenesis. Nephron progenitors are initially correctly specified in the mutant kidneys, with normal expression of several transcription factors known to be critical in progenitors, including Six2, Pax2, Sall1, and Wt1. However, there is premature loss of the nephron progenitor marker Cited1, marked apoptosis, and increased expression of the proapoptotic protein Bim shortly after the initial inductive events in early kidney development. Subsequently, there is a failure in ureteric bud branching and nephron progenitor differentiation. Taken together, our data demonstrate a previously undetermined requirement for miRNAs during early kidney organogenesis and indicate a crucial role for miRNAs in regulating the survival of this lineage.</p>
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<name sortKey="Chu, Jessica Y S" sort="Chu, Jessica Y S" uniqKey="Chu J" first="Jessica Y. S." last="Chu">Jessica Y. S. Chu</name>
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<name sortKey="Bodnar, Andrew J" sort="Bodnar, Andrew J" uniqKey="Bodnar A" first="Andrew J." last="Bodnar">Andrew J. Bodnar</name>
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<name sortKey="Kreidberg, Jordan A" sort="Kreidberg, Jordan A" uniqKey="Kreidberg J" first="Jordan A." last="Kreidberg">Jordan A. Kreidberg</name>
<name sortKey="Sims Lucas, Sunder" sort="Sims Lucas, Sunder" uniqKey="Sims Lucas S" first="Sunder" last="Sims-Lucas">Sunder Sims-Lucas</name>
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