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XB-ART-42768
BMC Dev Biol November 15, 2011; 11 5.

The nephrogenic potential of the transcription factors osr1, osr2, hnf1b, lhx1 and pax8 assessed in Xenopus animal caps.

Drews C , Senkel S , Ryffel GU .


Abstract
The three distinct types of kidneys, pronephros, mesonephros and metanephros, develop consecutively in vertebrates. The earliest form of embryonic kidney, the pronephros, is derived from intermediate mesoderm and the first expressed genes localized in the pronephros anlage are the transcription factors osr1, osr2, hnf1b, lhx1 and pax8, here referred to as the early nephrogenic transcription factors. However, the pathway inducing nephrogenesis and the network of theses factors are poorly understood. Treatment of the undifferentiated animal pole explant (animal cap) of Xenopus with activin A and retinoic acid induces pronephros formation providing a powerful tool to analyze key molecular events in nephrogenesis. We have investigated the expression kinetics of the early nephrogenic transcription factors in activin A and retinoic acid treated animal caps and their potential to induce pronephric differentiation. In treated animal caps, expression of osr1, osr2, hnf1b and lhx1 are induced early, whereas pax8 expression occurs later implying an indirect activation. Activin A alone is able to induce osr2 and lhx1 after three hours treatment in animal caps while retinoic acid fails to induce any of these nephrogenic transcription factors. The early expression of the five transcription factors and their interference with pronephros development when overexpressed in embryos suggest that these factors potentially induce nephrogenesis upon expression in animal caps. But no pronephros development is achieved by either overexpression of OSR1, by HNF1B injection with activin A treatment, or the combined application of LHX1 and PAX8, although they influenced the expression of several early nephrogenic transcription factors in some cases. In an additional approach we could show that HNF1B induces several genes important in nephrogenesis and regulates lhx1 expression by an HNF1 binding site in the lhx1 promoter. The early nephrogenic transcription factors play an important role in nephrogenesis, but have no pronephros induction potential upon overexpression in animal caps. They activate transcriptional cascades that partially reflect the gene activation initiated by activin A and retinoic acid. Significantly, HNF1B activates the lhx1 promoter directly, thus extending the known activin A regulation of the lhx1 gene via an activin A responsive element.

PubMed ID: 21281489
PMC ID: PMC3042965
Article link: BMC Dev Biol

Genes referenced: acta1 anxa13 cer1 chrd.1 cltrn cpn1 esd fgfr4 frmd6 gdnf gjb1 gsc hnf1a hnf1b hnf4a inhba lhx1 myc odc1 osr1 osr2 otx2 oxsr1 pax2 pax8 pcdh8.2 prl.2 prodh2 rbms1 rpl35a slc22a6 slc5a2 slc7a8 tfe3 tff3.7 trps1 ube3a wnt11 wnt11b wnt9b
Antibodies: Kidney Ab1 Kidney Ab2


Article Images: [+] show captions
References [+] :
Agulnick, Interactions of the LIM-domain-binding factor Ldb1 with LIM homeodomain proteins. 1996, Pubmed, Xenbase


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