Abstract
The auditory and vestibular organs of the inner ear and the neurons that innervate them originate from Sox2-positive and Notch-active neurosensory domains specified at early stages of otic development. Sox2 is initially present throughout the otic placode and otocyst, and then it becomes progressively restricted to a ventro-medial domain. Using gain- and loss-of-function approaches in the chicken otocyst, we show that these early changes in Sox2 expression are regulated in a dose-dependent manner by Wnt/beta-catenin signalling. Both high and very low levels of Wnt activity repress Sox2 and neurosensory competence. However, intermediate levels allow the maintenance of Sox2 expression and sensory organ formation. We propose that a dorso-ventral (high-to-low) gradient and wave of Wnt activity initiated at the dorsal rim of the otic placode progressively restricts Sox2 and Notch activity to the ventral half of the otocyst, thereby positioning the neurosensory competent domains in the inner ear.
Highlights
The inner ear is composed of several sensory organs populated with specialised mechanosensory ‘hair’ cells and their supporting cells
The cochlear duct, which extends from the ventral aspect of the inner ear, contains an auditory epithelium called the organ of Corti in mammals, or the basilar papilla in birds and reptiles
The consequences of reducing Wnt signalling were strikingly different along the dorso-ventral axis of the otocyst: in dorsal regions, it induced ectopic neurosensory territories, whilst in the ventral domains, it repressed Sox2 expression, suggesting that low levels of Wnt activity are required for prosensory specification
Summary
The inner ear is composed of several sensory organs populated with specialised mechanosensory ‘hair’ cells and their supporting cells. Forcing Notch activity leads to the formation of ectopic sensory patches (Pan et al, 2013; Pan et al, 2010; Daudet and Lewis, 2005; Hartman et al, 2010; Neves et al, 2011), suggesting that it is one of the key factors maintaining Sox and prosensory competence (reviewed in Daudet and Zak, 2020) Another candidate regulator of prosensory specification is Wnt signalling (reviewed in Zak et al, 2015), which relies on interactions between soluble Wnt ligands and their transmembrane Frizzled receptors to activate canonical and non-canonical branches of the Wnt pathway (Komiya and Habas, 2008). The consequences of reducing Wnt signalling were strikingly different along the dorso-ventral axis of the otocyst: in dorsal regions, it induced ectopic neurosensory territories, whilst in the ventral domains, it repressed Sox expression, suggesting that low levels of Wnt activity are required for prosensory specification. These data suggest that a dorso-ventral gradient of Wnt signalling acts upstream of Notch to position, in a dose-dependent manner, the neurosensory-competent domains of the otocyst
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