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Hoffmann, R. A wiki for the life sciences where authorship matters. Nature Genetics (2008)
 
 
 
 
 

Pax 2/8- regulated Gata 3 expression is necessary for morphogenesis and guidance of the nephric duct in the developing kidney.

The mammalian pro- and mesonephros are transient embryonic kidneys essential for urogenital system development. The nephric (Wolffian) duct, which is a central constituent of both structures, elongates caudally along a stereotypical path to reach the hindlimb level where it induces metanephros (adult kidney) formation, while the remaining duct gives rise to the male genital tract (epidydimis, vas deferens). The transcription factors Pax 2 and Pax 8 are essential for the initiation of pro- and mesonephros development. In a cDNA microarray screen for genes specifically expressed in the pro/mesonephros and regulated by Pax proteins, we identified Gata 3, a transcription factor gene associated with hypoparathyroidism, deafness and renal anomaly ( HDR) syndrome. Gata 3 is already expressed in the pronephric anlage, together with Pax 2 and Pax 8, suggesting that it may be a direct Pax 2/8 target gene. Inactivation of Gata 3 by insertion of an Ires-GFP reporter gene resulted in a massive increase in nephric duct cellularity, which was accompanied by enhanced cell proliferation and aberrant elongation of the nephric duct. Interestingly, however, the nephrogenic cord extended, with delayed kinetics, along the entire caudal path up to the level of the hindlimb bud, indicating that extension of the nephric duct and cord is controlled by different guidance cues. At the molecular level, the nephric duct of Gata 3(-/-) embryos is characterized by the loss of Ret expression and signaling, which may contribute to the guidance defect of the nephric duct. Together, these results define Gata 3 as a key regulator of nephric duct morphogenesis and guidance in the pro/mesonephric kidney.[1]

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