Emx2 and early hair cell development in the mouse inner ear

Abstract

Emx2 is a homeodomain protein that plays a critical role in inner ear development. Homozygous null mice die at birth with a range of defects in the CNS, renal system and skeleton. The cochlea is shorter than normal with about 60% fewer auditory hair cells. It appears to lack outer hair cells and some supporting cells are either absent or fail to differentiate. Many of the hair cells differentiate in pairs and although their hair bundles develop normally their planar cell polarity is compromised. Measurements of cell polarity suggest that classic planar cell polarity molecules are not directly influenced by Emx2 and that polarity is compromised by developmental defects in the sensory precursor population or by defects in epithelial cues for cell alignment. Planar cell polarity is normal in the vestibular epithelia although polarity reversal across the striola is absent in both the utricular and saccular maculae. In contrast, cochlear hair cell polarity is disorganized. The expression domain for Bmp4 is expanded and Fgfr1 and Prox1 are expressed in fewer cells in the cochlear sensory epithelium of Emx2 null mice. We conclude that Emx2 regulates early developmental events that balance cell proliferation and differentiation in the sensory precursor population.

Aberrant cochlear hair cell attachments caused by Nectin-3 deficiency result in hair bundle abnormalities

“…These results indicate that the changes in junction formation caused by the aberrant attachments between HCs result in the disruption of HC maturation associated with the abnormal phenotypes of the hair bundles in the Nectin-3 -/-auditory epithelium. Similar phenotypes of the hair bundles were reported in homeobox transcription factor Emx2-deficient mice and in mice mutant for the Notch ligands Dll1 and Jag2 (Holley et al, 2010;Kiernan et al, 2005). In these mice, HCs were attached to each other and lost their polarity.…”

Reconstruction of the Mouse Otocyst and Early Neuroblast Lineage at Single-Cell Resolution

“…Additional juxtapositions between other marker genes identified even more detailed descriptive expression patterns (Figure S5E). Finally, B6 cells represent a distinct sub-population of Wnt active cells that exclusively co-express the endolymphatic duct marker Wnt2b and newly identified Wnt7a, but not Wnt7b, and are also positive for Emx2 which previously was not detectable in the otocyst by in situ hybridization (Holley et al, 2010) (Figures 2D and S5F). …”

Role of chromatin remodeling gene Cecr2 in neurulation and inner ear development

“…The homeobox gene Emx2 is thought to regulate proliferation and differentiation of hair cell precursors, and Emx2 mutants show hair cell polarity defects (Holley et al, 2010) However, Emx2 mutants also show significant loss of OHCs and support cells, with remaining cells forming indistinct rows. The effect is similar throughout the cochlea, and not more disorganized apically as with Cecr2.…”