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First published online 3 July 2006
doi: 10.1242/dev.02458

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The Notch-effector HRT1 gene plays a role in glomerular development and patterning of the Xenopus pronephros anlagen

¹ Laboratoire d'Embryologie Moléculaire, Université Libre de Bruxelles, Institut de Biologie et de Médecine Moléculaires (IBMM), rue des Profs. Jeener et Brachet 12, B-6041 Gosselies, Belgium.
² DFG-Center of Molecular Physiology of the Brain, Department of Developmental Biochemistry, University of Göttingen, Justus-von-Liebig Weg 11, 37077 Göttingen, Germany.

^* Author for correspondence (e-mail: ebellefr{at}ulb.ac.be)

Accepted 25 May 2006

Notch signaling has been shown to play a role in cell fate decisions in the Xenopus pronephros anlagen. Here, we show that the Xenopus Hairy-related transcription factor (HRT) gene XHRT1, and the Hairy/Enhancer of split (HES) genes Xhairy1, Xhairy2b, esr9 and esr10, have distinct restricted dynamic expression patterns during pronephros development, and that their expression is regulated by Notch. XHRT1, which is the earliest and strongest gene expressed in the pronephric region, is initially transcribed predominantly in the forming glomus, where it is downregulated by antisense morpholino oligonucleotide inhibition of xWT1. Later, it is activated in the most dorsoanterior part of the pronephros anlagen that gives rise to the proximal tubules. In agreement with this dynamic expression profile, we found that early activation of Notch favors glomus, whereas only later activation promotes proximal tubule formation. We show that, among the bHLH-O factors tested, only XHRT1 efficiently inhibits distal tubule and duct formation, and that only its translational inhibition causes a reduction of the expression of proximal tubule and glomus markers. Using domain swap experiments, we found that the XHRT1 C-terminal region is crucial for its activity. Together, our results provide evidence that XHRT1 plays an important role in glomerular development and early proximodistal patterning that is distinct from those of the other pronephric bHLH repressors.

Key words: XHRT1, Notch, Pronephros

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