Suppression of neural fate and control of inner ear morphogenesis by<i>Tbx1</i>

TLDR

The inner ear sensory organs and VIIIth cranial ganglion neurons arise from an ectodermal placode that invaginates to form an otocyst. The study proposes that Tbx1 functions as a selector gene controlling neural and sensory organ fate specification in the otocyst. Tbx1 suppresses neurogenin‑1–mediated neural fate, is essential for proper expression of sensory‑organ genes Otx1 and Bmp4, and its loss causes dysregulated neural competence, duplicated VIIIth ganglion rudiments, and a hypoplastic inner ear lacking vestibular and cochlear structures.

Abstract

Inner ear sensory organs and VIIIth cranial ganglion neurons of the auditory/vestibular pathway derive from an ectodermal placode that invaginates to form an otocyst. We show that in the mouse otocyst epithelium, Tbx1 suppresses neurogenin 1-mediated neural fate determination and is required for induction or proper patterning of gene expression related to sensory organ morphogenesis (Otx1 and Bmp4, respectively). Tbx1 loss-of-function causes dysregulation of neural competence in otocyst regions linked to the formation of either mechanosensory or structural sensory organ epithelia. Subsequently, VIIIth ganglion rudiment form is duplicated posteriorly, while the inner ear is hypoplastic and shows neither a vestibular apparatus nor a coiled cochlear duct. We propose that Tbx1 acts in the manner of a selector gene to control neural and sensory organ fate specification in the otocyst.