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XB-ART-36489
Genes Dev. September 15, 2007; 21 (18): 2358-70.

The prepattern transcription factor Irx3 directs nephron segment identity.

Reggiani L , Raciti D , Airik R , Kispert A , Brändli AW .


Abstract
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.

PubMed ID: 17875669
PMC ID: PMC1973149
Article link: Genes Dev.

Genes referenced: atp1a1 fxyd2 gal.2 irx1 irx2 irx3 pax2 pou3f3 slc12a1 slc12a3 slc5a11 slc5a2 slc7a13

Morpholinos referenced: Irx1 MO2 Irx2 MO3 Irx2 MO4 Irx3 MO3 Irx3 MO4 irx1 MO1 irx2 MO5 irx3 MO1 irx3 MO5

References:
Aldaz, 2003, Pubmed[+]


Article Images: [+] show captions

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