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Development. November 1, 2009; 136 (21): 3585-95.

Notch activates Wnt-4 signalling to control medio-lateral patterning of the pronephros.

Naylor RW , Jones EA .

Previous studies have highlighted a role for the Notch signalling pathway during pronephrogenesis in the amphibian Xenopus laevis, and in nephron development in the mammalian metanephros, yet a mechanism for this function remains elusive. Here, we further the understanding of how Notch signalling patterns the early X. laevis pronephros anlagen, a function that might be conserved in mammalian nephron segmentation. Our results indicate that early phase pronephric Notch signalling patterns the medio-lateral axis of the dorso-anterior pronephros anlagen, permitting the glomus and tubules to develop in isolation. We show that this novel function acts through the Notch effector gene hrt1 by upregulating expression of wnt4. Wnt-4 then patterns the proximal pronephric anlagen to establish the specific compartments that span the medio-lateral axis. We also identified pronephric expression of lunatic fringe and radical fringe that is temporally and spatially appropriate for a role in regulating Notch signalling in the dorso-anterior region of the pronephros anlagen. On the basis of these results, along with data from previous publications, we propose a mechanism by which the Notch signalling pathway regulates a Wnt-4 function that patterns the proximal pronephric anlagen.

PubMed ID: 19793883
Article link: Development.
Grant support: G12713 Biotechnology and Biological Sciences Research Council , G1988 Biotechnology and Biological Sciences Research Council

Genes referenced: dll1 gal.2 gata3 gnl3 hey1 lfng lhx1 myh4 myh6 notch1 nphs1 odf3 rfng slc5a2 sst tbx2 tbxt wnt4 atp1b1

Morpholinos referenced: hey1 MO2 lfng MO1 lfng MO2 suclg2 MO1 wnt4 MO1

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