FGFR1-Frs2/3 Signalling Maintains Sensory Progenitors during Inner Ear Hair Cell Formation

Ono, Kazuya; Kita, Tomoko; Sato, Shigeru; O'Neill, Paul; Mak, Siu-Shan; Paschaki, Marie; Ito, Masataka; Gotoh, Noriko; Kawakami, Kiyoshi; Sasai, Yoshiki; Ladher, Raj K.
January 2014
PLoS Genetics;Jan2014, Vol. 10 Issue 1, p1
Academic Journal
Inner ear mechanosensory hair cells transduce sound and balance information. Auditory hair cells emerge from a Sox2-positive sensory patch in the inner ear epithelium, which is progressively restricted during development. This restriction depends on the action of signaling molecules. Fibroblast growth factor (FGF) signalling is important during sensory specification: attenuation of Fgfr1 disrupts cochlear hair cell formation; however, the underlying mechanisms remain unknown. Here we report that in the absence of FGFR1 signaling, the expression of Sox2 within the sensory patch is not maintained. Despite the down-regulation of the prosensory domain markers, p27Kip1, Hey2, and Hes5, progenitors can still exit the cell cycle to form the zone of non-proliferating cells (ZNPC), however the number of cells that form sensory cells is reduced. Analysis of a mutant Fgfr1 allele, unable to bind to the adaptor protein, Frs2/3, indicates that Sox2 maintenance can be regulated by MAP kinase. We suggest that FGF signaling, through the activation of MAP kinase, is necessary for the maintenance of sensory progenitors and commits precursors to sensory cell differentiation in the mammalian cochlea.


Related Articles

  • The Notch Ligand JAG1 Is Required for Sensory Progenitor Development in the Mammalian Inner Ear. Kiernan, Amy E.; Jingxia Xu; Gridley, Thomas; Beier, David // PLoS Genetics;Jan2006, Vol. 2 Issue 1, pe4 

    In mammals, six separate sensory regions in the inner ear are essential for hearing and balance function. Each sensory region is made up of hair cells, which are the sensory cells, and their associated supporting cells, both arising from a common progenitor. Little is known about the molecular...

  • Mammalian cochlear supporting cells can divide and trans-differentiate into hair cells. White, Patricia M.; Doetzlhofer, Angelika; Yun Shain Lee; Groves, Andrew K.; Segil, Neil // Nature;6/22/2006, Vol. 441 Issue 7096, p984 

    Sensory hair cells of the mammalian organ of Corti in the inner ear do not regenerate when lost as a consequence of injury, disease, or age-related deafness. This contrasts with other vertebrates such as birds, where the death of hair cells causes surrounding supporting cells to re-enter the...

  • Neurod1 Suppresses Hair Cell Differentiation in Ear Ganglia and Regulates Hair Cell Subtype Development in the Cochlea. Jahan, Israt; Pan, Ning; Kersigo, Jennifer; Fritzsch, Bernd // PLoS ONE;2010, Vol. 5 Issue 7, p1 

    Background: At least five bHLH genes regulate cell fate determination and differentiation of sensory neurons, hair cells and supporting cells in the mammalian inner ear. Cross-regulation of Atoh1 and Neurog1 results in hair cell changes in Neurog1 null mice although the nature and mechanism of...

  • What Stops the Inner Ear from Regenerating? Groves, Andy // Volta Review;Fall2010, Vol. 110 Issue 3, p465 

    Hearing loss is one of the most common disabilities in the United States. The most common form of hearing loss is caused by the death of cochlear hair cells in the organ of Corti and once lost, hair cells in humans and other mammals do not regenerate. In contrast, non-mammalian vertebrates, such...

  • Activated Notch Causes Deafness by Promoting a Supporting Cell Phenotype in Developing Auditory Hair Cells. Savoy-Burke, Grace; Gilels, Felicia A.; Pan, Wei; Pratt, Diana; Que, Jianwen; Gan, Lin; White, Patricia M.; Kiernan, Amy E. // PLoS ONE;Sep2014, Vol. 9 Issue 9, p1 

    Purpose: To determine whether activated Notch can promote a supporting cell fate during sensory cell differentiation in the inner ear. Methods: An activated form of the Notch1 receptor (NICD) was expressed in early differentiating hair cells using a Gfi1-Cre mouse allele. To determine the...

  • The Candidate Splicing Factor Sfswap Regulates Growth and Patterning of Inner Ear Sensory Organs. Moayedi, Yalda; Basch, Martin L.; Pacheco, Natasha L.; Gao, Simon S.; Wang, Rosalie; Harrison, Wilbur; Xiao, Ningna; Oghalai, John S.; Overbeek, Paul A.; Mardon, Graeme; Groves, Andrew K. // PLoS Genetics;Jan2014, Vol. 10 Issue 1, p1 

    The Notch signaling pathway is thought to regulate multiple stages of inner ear development. Mutations in the Notch signaling pathway cause disruptions in the number and arrangement of hair cells and supporting cells in sensory regions of the ear. In this study we identify an insertional...

  • The MYC Road to Hearing Restoration. Kopecky, Benjamin; Fritzsch, Bernd // Cells (2073-4409);Dec2012, Vol. 1 Issue 4, p667 

    Current treatments for hearing loss, the most common neurosensory disorder, do not restore perfect hearing. Regeneration of lost organ of Corti hair cells through forced cell cycle re-entry of supporting cells or through manipulation of stem cells, both avenues towards a permanent cure, require...

  • Ca2+ current-driven nonlinear amplification by the mammalian cochlea in vitro. Chan, Dylan K; Hudspeth, A J // Nature Neuroscience;Feb2005, Vol. 8 Issue 2, p149 

    An active process in the inner ear expends energy to enhance the sensitivity and frequency selectivity of hearing. Two mechanisms have been proposed to underlie this process in the mammalian cochlea: receptor potential-based electromotility and Ca2+-driven active hair-bundle motility. To link...

  • What Stops the Innner Ear From Regenerating? Groves, Andy; Segil, Neil // Hearing Health;Fall2012, Vol. 28 Issue 4, p30 

    The article discusses a Hearing Restoration Project (HRP) revealing the possible explanations behind mammals inability to regenerate hair cells in the cochlea after damage, as seen in birds. Results showed that supporting cells in a newborn mouse posses the ability to divide; however a...


Read the Article


Sorry, but this item is not currently available from your library.

Try another library?
Sign out of this library

Other Topics