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. 2021 Apr 30;100(Suppl 1):S1–S43. doi: 10.1055/a-1349-3824

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The Author(s). This is an open access article published by Thieme under the terms of the Creative Commons Attribution-NonDerivative-NonCommercial-License, permitting copying and reproduction so long as the original work is given appropriate credit. Contents may not be used for commercial purposes, or adapted, remixed, transformed or built upon. (https://creativecommons.org/licenses/by-nc-nd/4.0/).

This is an open-access article distributed under the terms of the Creative Commons Attribution-NonCommercial-NoDerivatives License, which permits unrestricted reproduction and distribution, for non-commercial purposes only; and use and reproduction, but not distribution, of adapted material for non-commercial purposes only, provided the original work is properly cited.

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Fig. 2 — The location of formation of the otic placode along the body axis is defined via the expression of fibroblast growth factors (FGF) from the neural tube ²⁰ . The release of FGF in the periotic mesoderm shortly before the development of the otic placode ²¹ leads to the expression of several transcription factors that are necessary for the development of the inner ear ²² ²³ . The orientation of the antero-posterior axis starts with the expression of FGF10, lunatic fringe (Lfng), delta 1, neurogenin1 (Ngn1), and neuronal differentiation factor (NeuroD1) in the anterior region of the invaginating otic placode. This gene expression pattern is limited to the anterior region of the otocyst. This limitation is mediated by Tbx1 that is exclusively expressed in the posterior part of the otocyst. The dorso-ventral axis depends on the WNT and SHH expression in the rhomb encephalon. WNT is expressed in the dorsal area and leads to upregulation of Dlx5, Dlx6, Hmx2, and Gbx2. These genes are responsible for the development of vestibular structures in the dorsal region of the otocyst. On the other hand, there is the expression of SHH from the notochord that determines the fate (auditory) of the cells in the ventral part of the otocyst by regulating the expression of the transcription factors Pax2, Ngn1, Lfng, NeuroD1, Sox2, and Six1. BMP (bone morphogenetic protein) and SHH inhibit each other so that BMP assumes a significant role in the morphogenesis of the inner ear. Illustration modified according to ²⁴ ²⁵ .