Tbx1 and Jag1 act in concert to modulate the fate of neurosensory cells of the mouse otic vesicle

Stephania Macchiarulo, Bernice E. Morrow

Research output: Contribution to journalArticle

2 Scopus citations

Abstract

The domain within the otic vesicle (OV) known as the neurosensory domain (NSD), contains cells that will give rise to the hair and support cells of the otic sensory organs, as well as the neurons that form the cochleovestibular ganglion (CVG). The molecular dynamics that occur at the NSD boundary relative to adjacent OV cells is not well defined. The Tbx1 transcription factor gene expression pattern is complementary to the NSD, and inactivation results in expansion of the NSD and expression of the Notch ligand, Jag1 mapping, in part of the NSD. To shed light on the role of Jag1 in NSD development, as well as to test whether Tbx1 and Jag1 might genetically interact to regulate this process, we inactivated Jag1 within the Tbx1 expression domain using a knock-in Tbx1Cre allele. We observed an enlarged neurogenic domain marked by a synergistic increase in expression of NeuroD and other proneural transcription factor genes in double Tbx1 and Jag1 conditional loss-of-function embryos. We noted that neuroblasts preferentially expanded across the medial-lateral axis and that an increase in cell proliferation could not account for this expansion, suggesting that there was a change in cell fate. We also found that inactivation of Jag1 with Tbx1Cre resulted in failed development of the cristae and semicircular canals, as well as notably fewer hair cells in the ventral epithelium of the inner ear rudiment when inactivated on a Tbx1 null background, compared to Tbx1Cre/− mutant embryos. We propose that loss of expression of Tbx1 and Jag1 within the Tbx1 expression domain tips the balance of cell fates in the NSD, resulting in an overproduction of neuroblasts at the expense of non-neural cells within the OV.

Original languageEnglish (US)
Pages (from-to)1472-1482
Number of pages11
JournalBiology Open
Volume6
Issue number10
DOIs
StatePublished - Oct 15 2017

Keywords

  • Inner ear
  • Jag1
  • Neurosensory
  • Notch
  • Otic vesicle
  • Tbx1

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Agricultural and Biological Sciences(all)

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