Abstract:
:Branching morphogenesis is a developmental process characteristic of many organ systems. Specifically, during renal branching morphogenesis, its been postulated that the final number of nephrons formed is one key clinical factor in the development of hypertension in adulthood. As it has been established that BMPs regulate, in part, renal activity of p38 MAP kinase (p38(MAPK)) and it has demonstrated that the cytoplasmic protein Neurotrophin Receptor MAGE homologue (NRAGE) augments p38(MAPK) activation, it was hypothesized that a decrease in the expression of NRAGE during renal branching would result in decreased branching of the UB that correlated with changes in p38(MAPK) activation. To verify this, the expression of NRAGE was reduced in ex vivo kidney explants cultures using antisense morpholino. Morpholino treated ex vivo kidney explants expression were severely stunted in branching, a trait that was rescued with the addition of exogenous GDNF. Renal explants also demonstrated a precipitous drop in p38(MAPK) activation that too was reversed in the presence of recombinant GDNF. RNA profiling of NRAGE diminished ex vivo kidney explants resulted in altered expression of GDNF, Ret, BMP7 and BMPRIb mRNAs. Our results suggested that in early kidney development NRAGE might have multiple roles during renal branching morphogenesis through association with both the BMP and GDNF signaling pathways.
journal_name
Mech Devjournal_title
Mechanisms of developmentauthors
Nikopoulos GN,Martins JF,Adams TL,Karaczyn A,Adams D,Vary C,Oxburgh L,Verdi JMdoi
10.1016/j.mod.2009.02.005subject
Has Abstractpub_date
2009-05-01 00:00:00pages
337-49issue
5-6eissn
0925-4773issn
1872-6356pii
S0925-4773(09)00031-8journal_volume
126pub_type
杂志文章abstract::In multicellular organisms, very little is known about the role of mRNA stability in development, and few proteins involved in degradation pathways have been characterized. We have identified the Drosophila homologue of XRN1, which is the major cytoplasmic 5'-3' exoribonuclease in Saccharomyces cerevisiae. The protein...
journal_title:Mechanisms of development
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journal_title:Mechanisms of development
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journal_title:Mechanisms of development
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journal_title:Mechanisms of development
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journal_title:Mechanisms of development
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journal_title:Mechanisms of development
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journal_title:Mechanisms of development
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journal_title:Mechanisms of development
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