Role of Gbx2 and Otx2 in the formation of cochlear ganglion and endolymphatic duct

Abstract

The boundary of gene expression of transcription factors often plays a role in making a signaling center in development. In the otic vesicle, Gbx2 is expressed in the dorso-medial region including the endolymphatic duct, and Otx2 in the ventral region. Fgf10 is expressed between their expression boundaries, and the cochleovestibular ganglion develops close to the medial side of the Fgf10 expressing domain. Similar expression patterns are observed in the central nervous system, where Otx2 and Gbx2 expression abut at the mid-hindbrain boundary, and the repressive interaction between Otx2 and Gbx2 defines the mid-hindbrain boundary. These analogous expression patterns raise a question about the role of the interaction between Gbx2 and Otx2 in the otic vesicle. To address this, we misexpressed Gbx2 and Otx2 to the otic epithelium. Ectopic Gbx2 expression could repress Otx2 expression and vice versa. In addition, Fgf10 expression was repressed and cochlear ganglion formation was interfered with. Moreover, endolymphatic duct was severely hypomorphic in the Otx2 misexpressing embryos. These results suggest that the interaction between Gbx2 and Otx2 in developing inner ear defines Fgf10 expression domain to induce the cochlear ganglion. It is also suggested that Gbx2 expression is important for the formation of the endolymphatic duct.

Conditional deletion of N‐Myc disrupts neurosensory and non‐sensory development of the ear

“…Lmx1a , and Otx1. Otx2 regulates Fgf10 (an upstream activator of N-Myc ) expression in the otic placode of chicken (Bok et al, 2005; Miyazaki et al, 2006) and a link between increased levels of Otx2 and N-Myc was shown in meduloblastomas, suggesting that Otx2 and N-Myc may form a feedback loop (Adamson et al, 2010). Otx2 is found in the cochlea while Otx1 is present in the vestibular epithelia (Morsli et al, 1999) and while there appears to be a possible connection between Otx2 and N-Myc , the interaction between Otx1 and N-Myc remains unstudied.…”

The ATP-dependent chromatin remodeling enzyme CHD7 regulates pro-neural gene expression and neurogenesis in the inner ear

“…Furthermore, Otx2 is an important early otic patterning gene and is required for establishment of the neurogenic domain by repressing Fgf10 expression (Miyazaki et al, 2006). As both Otx2 and Fgf10 expression are absent from Chd7 null otocysts, CHD7 may regulate Fgf10 in an OTX2-dependent manner.…”

“…We tested whether reduced CHD7 impacts expression of genes implicated in E9.5-E10.5 otocyst patterning. Otx2, which regulates cochlear patterning and ganglion development (Miyazaki et al, 2006;Morsli et al, 1999), was retained in E10.5 Chd7 Gt/+ and conditional heterozygotes, but was absent from conditional null and Chd7…”

Axial patterning in the developing vertebrate inner ear

“…In addition, ventral otic derivatives-the cochlea and spiral ganglion-are malformed in both mutants, even though Gbx2 is not expressed in ventral otic domains. This may be due, at least in part, to mutually repressive interactions between Gbx2 and Otx2 (Lin et al, 2005;Choo et al, 2006;Miyazaki et al, 2006). Gbx2 is required for Wnt2b and medial Dlx5/6 expression, which is also lost in kr/Mafb mutants (Lin et al, 2005;Choo et al, 2006).…”