Abstract
Hmga2 protein belongs to the non-histone chromosomal high-mobility group (HMG) protein family. HMG proteins have been shown to function as architectural transcription regulators, facilitating enhanceosome formation on a variety of mammalian promoters. Hmga2 are expressed at high levels in embryonic and transformed cells. Terminally differentiated cells, however, have been reported to express only minimal, if any, Hmga2. Our previous affymetrix array data showed that Hmga2 is expressed in the developing and adult mammalian cochleas. However, the spatio-temporal expression pattern of Hmga2 in the murine cochlea remained unknown. In this study, we report the expression of Hmga2 in developing and adult cochleas using immunohistochemistry and quantitative real time PCR analysis. Immunolabeling of Hmga2 in the embryonic, postnatal, and mature cochleas showed broad Hmga2 expression in embryonic cochlea (E14.5) at the level of the developing organ of Corti in differentiating hair cells, supporting cells, in addition to immature cells in the GER and LER areas. By postnatal stage (P0–P3), Hmga2 is predominantly expressed in the hair and supporting cells, in addition to cells in the LER area. By P12, Hmga2 immunolabeling is confined to the hair cells and supporting cells. In the adult ear, Hmga2 expression is maintained in the hair and supporting cell subtypes (i.e. Deiters’ cells, Hensen cells, pillar cells, inner phalangeal and border cells) in the cochlear epithelium. Using quantitative real time PCR, we found a decrease in transcript level for Hmga2 comparable to other known inner ear developmental genes (Sox2, Atoh1, Jagged1 and Hes5) in the cochlear epithelium of the adult relative to postnatal ears. These data provide for the first time the tissue-specific expression and transcription level of Hmga2 during inner ear development and suggest its potential dual role in early differentiation and maintenance of both hair and supporting cell phenotypes.
Highlights
The mammalian inner ear is an intricate organ responsible for the perception of sound and balance
Previous histological studies suggest that during cochlear embryonic development, whereas the inner hair cells derive from multivillous columnar epithelial precursor cells located in the proximal region of the greater epithelial ridge (GER), the outer hair cells derive from the most distal cells in the lesser epithelial ridge (LER)
The quantitative real time PCR (qRT-PCR) results (Fig. 7) indicated that similar to the expression levels of other known inner ear differentiation genes (i.e. Sox2, Atoh1, Jagged1 and Hes5), Hmga2 transcripts are downregulated in the cochlear sensory epithelium of the adult (P60) when compared to the early postnatal (P3) mice. These results indicate that Hmga2 is expressed in the developing cochlea and that its expression level changes as the cochlea matures
Summary
The mammalian inner ear is an intricate organ responsible for the perception of sound and balance. Several lines of evidences reported that early expressed inner ear genes with long-term lasting expressions and specific effects on all or subsets of placode progenitor cells are Eya1/Six, Pax2/8, Gata and Sox2 [7,8,9] which may help regulate neurosensory development through gene expression regulation [10,11]. While these genes have a dose and/or time dependent preferential effect on cochlear neurosensory development, Sox has a more dominant effect on all neurosensory precursors [12,13]. It has been reported that Sox has a refined interaction with downstream genes such as the bHLH gene Atoh and shown to be required for its expression but will be downregulated following the expression of Atoh in the inner ear sensory hair cells [14]
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