Divergent roles for Wnt/β-catenin signaling in epithelial maintenance and breakdown during semicircular canal formation

The morphogenetic program that shapes the three semicircular canals (SSCs) must be executed with extreme precision to satisfy their complex vestibular function. The SSCs emerge from epithelial outgrowths of the dorsal otocyst, the central regions of which fuse and resorb to leave three fluid-filled...

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Veröffentlicht in:Development (Cambridge) 2013-04, Vol.140 (8), p.1730-1739
Hauptverfasser: Rakowiecki, Staci, Epstein, Douglas J
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description The morphogenetic program that shapes the three semicircular canals (SSCs) must be executed with extreme precision to satisfy their complex vestibular function. The SSCs emerge from epithelial outgrowths of the dorsal otocyst, the central regions of which fuse and resorb to leave three fluid-filled canals. The Wnt/β-catenin signaling pathway is active at multiple stages of otic development, including during vestibular morphogenesis. How Wnt/β-catenin functionally integrates with other signaling pathways to sculpt the SSCs and their sensory patches is unknown. We used a genetic strategy to spatiotemporally modulate canonical Wnt signaling activity during SSC development in mice. Our findings demonstrate that Wnt/β-catenin signaling functions in a multifaceted manner during SSC formation. In the early phase, Wnt/β-catenin signaling is required to preserve the epithelial integrity of the vertical canal pouch perimeter (presumptive anterior and posterior SSCs) by establishing a sensory-dependent signaling relay that maintains expression of Dlx5 and opposes expression of the fusion plate marker netrin 1. Without this Wnt signaling activity the sensory to non-sensory signaling cascade fails to be activated, resulting in loss of vestibular hair and support cells and the anterior and posterior SSCs. In the later phase, Wnt/β-catenin signaling becomes restricted to the fusion plate where it facilitates the timely resorption of this tissue. Mosaic recombination of β-catenin in small clusters of canal pouch cells prevents their resorption, causing instead the formation of ectopic SSCs. Together, these disparate functions of the Wnt/β-catenin pathway in epithelial maintenance and resorption help regulate the size, shape and number of SSCs.
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Without this Wnt signaling activity the sensory to non-sensory signaling cascade fails to be activated, resulting in loss of vestibular hair and support cells and the anterior and posterior SSCs. In the later phase, Wnt/β-catenin signaling becomes restricted to the fusion plate where it facilitates the timely resorption of this tissue. Mosaic recombination of β-catenin in small clusters of canal pouch cells prevents their resorption, causing instead the formation of ectopic SSCs. 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subjects Animals
beta Catenin - metabolism
beta-Galactosidase
Bromodeoxyuridine
Epithelium - embryology
Gene Expression Regulation, Developmental - genetics
Gene Expression Regulation, Developmental - physiology
Homeodomain Proteins - metabolism
Immunohistochemistry
In Situ Hybridization
Mice
Morphogenesis - physiology
Nerve Growth Factors - metabolism
Netrin-1
Semicircular Canals - embryology
Tumor Suppressor Proteins - metabolism
Wnt Signaling Pathway - physiology
title Divergent roles for Wnt/β-catenin signaling in epithelial maintenance and breakdown during semicircular canal formation
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