TAK1 Expression in the Cochlea: A Specific Marker for Adult Supporting Cells

Abstract

Transforming growth factor-β-activated kinase-1 (TAK1) is a mitogen activated protein kinase kinase kinase that is involved in diverse biological roles across species. Functioning downstream of TGF-β and BMP signaling, TAK1 mediates the activation of the c-Jun Nterminal kinase signaling pathway, serves as the target of pro-inflammatory cytokines, such as TNF-α, mediates NF-κβ activation, and plays a role in Wnt/Fz signaling in mesenchymal stem cells. Expression of TAK1 in the cochlea has not been defined. Data mining of previously published murine cochlear gene expression databases indicated that TAK1, along with TAK1 interacting proteins 1 (TAB1), and 2 (TAB2), is expressed in the developing and adult cochlea. The expression of TAK1 in the developing cochlea was confirmed using RT-PCR and immunohistochemistry. Immunolabeling of TAK1 in embryonic, neonatal, and mature cochleas via DAB chromogenic and fluorescent immunohistochemistry indicated that TAK1 is broadly expressed in both the developing otocyst and periotic mesenchyme at E12.5 but becomes more restricted to specific types of supporting cells as the organ of Corti matures. By P1, TAK1 immunolabeling is found in cells of the stria vascularis, hair cells, supporting cells, and Kölliker's organ. By P16, TAK1 labeling is limited to cochlear supporting cells. In the adult cochlea, TAK1 immunostaining is only present in the cytoplasm of Deiters' cells, pillar cells, inner phalangeal cells, and inner border cells, with no expression in any other cochlear cell types. While the role of TAK1 in the inner ear is unclear, TAK1 expression may be used as a novel marker for specific sub-populations of supporting cells.

Inner ear supporting cells: Rethinking the silent majority

“…The glutamate-aspartate transporter GLAST is expressed on inner border and inner phalangeal cells [88]. Tak1 is expressed by all organ of Corti supporting cells except for Hensen’s cells [89]. Aquaporin4 is found in Hensen’s cells [90].…”

Biotechnology in the Treatment of Sensorineural Hearing Loss: Foundations and Future of Hair Cell Regeneration

“…R. Snyder et al, 2010). Additionally, several laboratories are developing cell specific delivery systems for genes such as atoh1 (Parker, Jiang, Adams, & Edge, 2010). This research is continuing at a rapid rate and is being conducted by teams of talented researchers.…”

Early appearance of key transcription factors influence the spatiotemporal development of the human inner ear

“…Although vestibular hair cells do possess low levels of regenerative capacity, this, however, declines with aging and is not adequate to cope with hair cell loss (Burns and Stone 2017;Rauch et al 2001). Sustained efforts to understand processes underlying inner ear development using murine models have revealed roles for several quintessential transcription factors like leucine-rich repeat-containing G protein-coupled receptor 5 (LGR5) (Bramhall et al 2014), transforming growth factor-β-activated kinase-1 (TAK1) (Parker et al 2011), SOX2 (Dvorakova et al 2016), and GATA binding protein 3 (GATA3) (Karis et al 2001). The expression profiles of these transcriptional factors and their functionality in human inner ear development are not currently clear.…”