Morpholinos for splice modificatio

Morpholinos for splice modification


Notch activates Wnt-4 signalling to control medio-lateral patterning of the pronephros
Richard W. Naylor, Elizabeth A. Jones


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.


  • We thank Peter Vize for helpful comments and the nephrin probe, Anna Philpott for Notch-ICD, DeltaSTU and MHC constructs, Kelly McLaughlin for the Notch-1 probe, Eric Bellefroid for the HRT-1 in situ probe and inducible constructs, Surinder Bhamra for performing histological sections and Paul Jarrett for maintenance of frogs. We thank unknown reviewers for improving the manuscript. This work was supported by BBSRC grants G1988, G12713.

    • Accepted September 1, 2009.
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