Hearing crosstalk: the molecular conversation orchestrating inner ear dorsoventral patterning

5 years ago

Hearing crosstalk: the molecular conversation orchestrating inner ear dorsoventral patterning

Gary C. Schoenwolf, Sho Ohta

The inner ear is a structurally and functionally complex organ that functions in balance and hearing. It originates during neurulation as a localized thickened region of rostral ectoderm termed the otic placode, which lies adjacent to the developing caudal hindbrain. Shortly after the otic placode forms, it invaginates to delineate the otic cup, which quickly pinches off of the surface ectoderm to form a hollow spherical vesicle called the otocyst; the latter gives rise dorsally to inner ear vestibular components and ventrally to its auditory component. Morphogenesis of the otocyst is regulated by secreted proteins, such as WNTs, BMPs, and SHH, which determine its dorsoventral polarity to define vestibular and cochlear structures and sensory and nonsensory cell fates. In this review, we focus on the crosstalk that occurs among three families of secreted molecules to progressively polarize and pattern the developing otocyst. For further resources related to this article, please visit the WIREs website. Summary of the known otocyst transcription factors regulated by crosstalk among three families of secreted proteins during dorsoventral (DV) patterning. DV patterning of the otocyst is orchestrated by crosstalk among three families of secreted proteins that regulate the expression of transcription factors in a temporospatial manner. BMP signaling, which is required for the development of the dorsal (vestibular) component of the inner ear, upregulates the expression of two transcription factors, Dlx5 and Hmx3, both of which are essential for vestibular development. WNT and BMP signaling partner to induce Dlx5 expression in the dorsolateral wall of the otocyst, whereas WNT signaling acts alone in the dorsomedial wall to regulate the expression of Gbx2, which in turn seems to be required for Dlx5 expression. SHH signaling, which is required for the development of the ventral (cochlear) component of the inner ear, upregulates the expression of two transcription factors, Pax2 and Otx2, both of which are essential for cochlear development. The expression of transcription factors in the dorsal and ventral otocyst also is inhibited by secreted factors, with BMP signaling downregulating Otx2 expression and SHH signaling downregulating Hmx3 expression and arguably downregulating Dlx5 expression.

Publisher URL: http://onlinelibrary.wiley.com/resolve/doi

DOI: 10.1002/wdev.302