Deafness: Lack of regulation encourages hair cell growth

  title={Deafness: Lack of regulation encourages hair cell growth},
  author={Y. Raphael and Donna M. Martin},
  journal={Gene Therapy},
Hearing loss and balance disorders affect millions of people worldwide. In most cases, degeneration of hair cells (HCs), the sensory cells of the cochlea and the vestibular end organs is the cause of these disorders. New auditory HCs do not develop after embryonic development, and once lost, these cells are not replaced. So it is truly exciting when experimental attempts to generate new HCs succeed. In a paper published in Science Express on January 13, Sage et al show that conditional deletion… 



Auditory hair cell replacement and hearing improvement by Atoh1 gene therapy in deaf mammals

It is reported that Atoh1, a gene also known as Math1 encoding a basic helix-loop-helix transcription factor and key regulator of hair cell development, induces regeneration of hair cells and substantially improves hearing thresholds in the mature deaf inner ear after delivery to nonsensory cells through adenovectors.

Generation of hair cells by stepwise differentiation of embryonic stem cells

It is demonstrated that cells that express markers characteristic of hair cells differentiate from embryonic stem cell-derived progenitors, and that integrated cells start expressing hair cell markers and display hair bundles when situated in cochlear or vestibular sensory epithelia in vivo.

Proliferation of Functional Hair Cells in Vivo in the Absence of the Retinoblastoma Protein

By profiling gene expression in developing mouse vestibular organs, the retinoblastoma protein (pRb) is identified as a candidate regulator of cell cycle exit in hair cells and Manipulation of the pRb pathway may ultimately lead to mammalian hair cell regeneration.

Gene disruption of p27(Kip1) allows cell proliferation in the postnatal and adult organ of corti.

It is reported that the cyclin-dependent kinase inhibitor p27(Kip1) is selectively expressed in the supporting-cell population of the organ of Corti, and may provide an important pathway for inducing hair-cell regeneration in the mammalian hearing organ.

Pluripotent stem cells from the adult mouse inner ear

It is shown that the adult utricular sensory epithelium contains cells that display the characteristic features of stem cells, and these inner ear stem cells have the capacity for self-renewal, and form spheres that express marker genes of the developing inner ear and the nervous system.

Overexpression of Math1 induces robust production of extra hair cells in postnatal rat inner ears

It is reported here that overexpression of Math1, a mouse homolog of the Drosophila gene atonal, in postnatal rat cochlear explant cultures resulted in extra hair cells, and immature postnatal mammalian inner ears retained the competence to generate new hair cells.

p27(Kip1) links cell proliferation to morphogenesis in the developing organ of Corti.

P27(Kip1) expression is induced in the primordial organ of Corti between E12 and E14, correlating with the cessation of cell division of the progenitors of the hair cells and supporting cells, providing a link between developmental control of cell proliferation and the morphological development of the inner ear.

Retinoblastoma: Revisiting the model prototype of inherited cancer

  • D. LohmannB. Gallie
  • Medicine
    American journal of medical genetics. Part C, Seminars in medical genetics
  • 2004
Current knowledge on the relations between the genotype and phenotypic expression is summarized and detailed analysis of genotype–phenotype relations shows that hereditary retinoblastoma has features of a complex trait.