Maternal xNorrin, a Canonical Wnt Signaling Agonist and TGF-β Antagonist, Controls Early Neuroectoderm Specification in Xenopus

Suhong Xu,Wei Wu,Juan Liang,Jian Zhang,Feng Cheng,Derek L Stemple

doi:10.1371/journal.pbio.1001286

Abstract

Author SummaryA key step during early embryogenesis is the generation of neural precursors, which later form the central nervous system. In vertebrates, this process requires proper dorsal–ventral axis specification, and we know that the canonical Wnt and BMP signaling pathways help pattern the dorsal ectoderm. In this study, we examine other factors that are involved in neuroectoderm development in the frog species Xenopus laevis. We find that maternal Xenopus Norrin (xNorrin) is required for canonical Wnt signaling in the dorsal ectoderm, functions upstream of neural inducers, and is required for neural formation. We also find that xNorrin not only activates Wnt signaling, but also inhibits BMP/Nodal-related signaling. In humans, mutations in Norrin cause Norrie disease. Using Norrin mutants identified in patients with Norrie disease, we find that some Norrin mutants fail to inhibit BMP/Nodal-related signaling (specifically, TGF-β) but retain the ability to activate the Wnt pathway, suggesting that loss of TGF-β inhibition may contribute to Norrie disease development.

Highlights

Dorsal–ventral axis specification is one of the earliest patterning events in the embryo
This process requires proper dorsal– ventral axis specification, and we know that the canonical Wnt and BMP signaling pathways help pattern the dorsal ectoderm
We find that maternal Xenopus Norrin is required for canonical Wnt signaling in the dorsal ectoderm, functions upstream of neural inducers, and is required for neural formation

Summary

Introduction

Dorsal–ventral axis specification is one of the earliest patterning events in the embryo. Current evidence strongly suggests that the canonical Wnt signaling pathway, operating at blastula stages, plays a critical role in dorsal specification [1]. Heasman and colleagues provided strong evidence that vegetally localized maternal Wnt cooperates with Wnt5A to activate the canonical Wnt pathway and is required for dorsal axis formation [5,6,7]. Previous studies suggested that Wnt pathway components may be transferred beyond 30u to the dorsal animal region [8,9]. It remains unknown whether such movements can fully account for Wnt activation in dorsal animal cells, and it is unclear how these movements precisely regulate the earliest steps of neuroectoderm formation in the blastula

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