Lack of <i>Rbl</i>1/p107 Effects on Cell Proliferation and Maturation in the Inner Ear

Abstract

Loss of postnatal mammalian auditory hair cells (HCs) is irreversible. Earlier studies have highlighted the importance of the Retinoblastoma family of proteins (pRBs) ( i.e ., Rb 1, Rbl 1/p107, and Rbl 2/p130) in the auditory cells’ proliferation and emphasized our lack of information on their specific roles in the auditory system. We have previously demonstrated that lack of Rbl 2/p130 moderately affects HCs’ and supporting cells’ (SCs) proliferation. Here, we present evidence supporting multiple roles for Rbl 1/p107 inthe developing and mature mouse organ of Corti (OC). Like other pRBs, Rbl 1/ p107 is expressed in the OC, particularly in the Hensen’s and Deiters’ cells. Moreover, Rbl 1/ p107 impacts maturation and postmitotic quiescence of HCs and SCs, as evidenced by enhanced numbers of these cells and the presence of dividing cells in the postnatal Rbl 1/ p107 －/－ OC. These findings were further supported by microarray and bioinformatics analyses, suggesting downregulation of several bHLH molecules, as well as activation of the Notch/Hes/Hey signaling pathway in homozygous Rbl 1/ p107 mutant mice. Physiological assessments and detection of ectopic HC marker expression in postnatal spiral ganglion neurons (SGNs) provided evidence for incomplete cell maturation and differentiation in Rbl 1/ p107 ﹣/﹣ OC. Collectively, the present study highlights an important role for Rbl 1/ p107 inOC cell differentiation and maturation, which is distinct from other pRBs.