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XB-ART-37108
PLoS Genet October 1, 2007; 3 (10): 1922-38.

The cdx genes and retinoic acid control the positioning and segmentation of the zebrafish pronephros.

Wingert RA , Selleck R , Yu J , Song HD , Chen Z , Song A , Zhou Y , Thisse B , Thisse C , McMahon AP , Davidson AJ .


Abstract
Kidney function depends on the nephron, which comprises a blood filter, a tubule that is subdivided into functionally distinct segments, and a collecting duct. How these regions arise during development is poorly understood. The zebrafish pronephros consists of two linear nephrons that develop from the intermediate mesoderm along the length of the trunk. Here we show that, contrary to current dogma, these nephrons possess multiple proximal and distal tubule domains that resemble the organization of the mammalian nephron. We examined whether pronephric segmentation is mediated by retinoic acid (RA) and the caudal (cdx) transcription factors, which are known regulators of segmental identity during development. Inhibition of RA signaling resulted in a loss of the proximal segments and an expansion of the distal segments, while exogenous RA treatment induced proximal segment fates at the expense of distal fates. Loss of cdx function caused abrogation of distal segments, a posterior shift in the position of the pronephros, and alterations in the expression boundaries of raldh2 and cyp26a1, which encode enzymes that synthesize and degrade RA, respectively. These results suggest that the cdx genes act to localize the activity of RA along the axis, thereby determining where the pronephros forms. Consistent with this, the pronephric-positioning defect and the loss of distal tubule fate were rescued in embryos doubly-deficient for cdx and RA. These findings reveal a novel link between the RA and cdx pathways and provide a model for how pronephric nephrons are segmented and positioned along the embryonic axis.

PubMed ID: 17953490
PMC ID: PMC2042002
Article link: PLoS Genet

Genes referenced: aldh1a2 aqp3 cdh17 cdx4 cyp26a1 dct egr2 fubp1 gata3 myh6 myod1 rfx2 slc12a1 slc13a1 slc9a3 sult1a1 trpm7


Article Images: [+] show captions
References [+] :
Anzenberger, Elucidation of megalin/LRP2-dependent endocytic transport processes in the larval zebrafish pronephros. 2006, Pubmed, Xenbase


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