Document Detail


The prepattern transcription factor Irx3 directs nephron segment identity.
MedLine Citation:
PMID:  17875669     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
The nephron, the basic structural and functional unit of the vertebrate kidney, is organized into discrete segments, which are composed of distinct renal epithelial cell types. Each cell type carries out highly specific physiological functions to regulate fluid balance, osmolarity, and metabolic waste excretion. To date, the genetic basis of regionalization of the nephron has remained largely unknown. Here we show that Irx3, a member of the Iroquois (Irx) gene family, acts as a master regulator of intermediate tubule fate. Comparative studies in Xenopus and mouse have identified Irx1, Irx2, and Irx3 as an evolutionary conserved subset of Irx genes, whose expression represents the earliest manifestation of intermediate compartment patterning in the developing vertebrate nephron discovered to date. Intermediate tubule progenitors will give rise to epithelia of Henle's loop in mammals. Loss-of-function studies indicate that irx1 and irx2 are dispensable, whereas irx3 is necessary for intermediate tubule formation in Xenopus. Furthermore, we demonstrate that misexpression of irx3 is sufficient to direct ectopic development of intermediate tubules in the Xenopus mesoderm. Taken together, irx3 is the first gene known to be necessary and sufficient to specify nephron segment fate in vivo.
Authors:
Luca Reggiani; Daniela Raciti; Rannar Airik; Andreas Kispert; André W Brändli
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Genes & development     Volume:  21     ISSN:  0890-9369     ISO Abbreviation:  Genes Dev.     Publication Date:  2007 Sep 
Date Detail:
Created Date:  2007-09-18     Completed Date:  2007-10-25     Revised Date:  2009-11-18    
Medline Journal Info:
Nlm Unique ID:  8711660     Medline TA:  Genes Dev     Country:  United States    
Other Details:
Languages:  eng     Pagination:  2358-70     Citation Subset:  IM    
Affiliation:
Department of Chemistry and Applied Biosciences, Institute of Pharmaceutical Sciences, ETH Zurich, CH-8093, Zurich, Switzerland.
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MeSH Terms
Descriptor/Qualifier:
Animals
Body Patterning / genetics*
Embryo, Nonmammalian
Gene Expression Regulation, Developmental
Homeodomain Proteins / physiology*
Kidney Tubules / embryology
Mice
Models, Biological
Nephrons / embryology*
Transcription Factors / physiology*
Xenopus / embryology*,  genetics
Chemical
Reg. No./Substance:
0/Homeodomain Proteins; 0/Transcription Factors; 0/Xiro3 protein, Xenopus
Comments/Corrections

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