1. Academic Validation
  2. Regulation of otocyst patterning by Tbx2 and Tbx3 is required for inner ear morphogenesis in the mouse

Regulation of otocyst patterning by Tbx2 and Tbx3 is required for inner ear morphogenesis in the mouse

  • Development. 2021 Apr 15;148(8):dev195651. doi: 10.1242/dev.195651.
Marina Kaiser 1 Irina Wojahn 1 Carsten Rudat 1 Timo H Lüdtke 1 Vincent M Christoffels 2 Anne Moon 3 4 Andreas Kispert 1 Mark-Oliver Trowe 1
Affiliations

Affiliations

  • 1 Institute for Molecular Biology, Medizinische Hochschule Hannover, 30625 Hannover, Germany.
  • 2 Department of Anatomy, Embryology and Physiology, Academic Medical Center, University of Amsterdam, 1105 AZ Amsterdam, The Netherlands.
  • 3 Department of Molecular and Functional Genomics, Weis Center for Research, Geisinger Clinic, Danville, PA 17822, USA.
  • 4 Department of Human Genetics, University of Utah School of Medicine, Salt Lake City, UT 84112, USA.
Abstract

All epithelial components of the inner ear, including sensory hair cells and innervating afferent neurons, arise by patterning and differentiation of epithelial progenitors residing in a simple sphere, the otocyst. Here, we identify the transcriptional repressors TBX2 and TBX3 as novel regulators of these processes in the mouse. Ablation of Tbx2 from the otocyst led to cochlear hypoplasia, whereas loss of Tbx3 was associated with vestibular malformations. The loss of function of both genes (Tbx2/3cDKO) prevented inner ear morphogenesis at midgestation, resulting in indiscernible cochlear and vestibular structures at birth. Morphogenetic impairment occurred concomitantly with increased Apoptosis in ventral and lateral regions of Tbx2/3cDKO otocysts around E10.5. Expression analyses revealed partly disturbed regionalisation, and a posterior-ventral expansion of the neurogenic domain in Tbx2/3cDKO otocysts at this stage. We provide evidence that repression of FGF signalling by TBX2 is important to restrict neurogenesis to the anterior-ventral otocyst and implicate another T-box factor, TBX1, as a crucial mediator in this regulatory network.

Keywords

Cochlea; FGF; Morphogenesis; Otic neurogenesis; Otic vesicle; Tbx1.

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