Regulation of cell fate and patterning in the developing mammalian cochlea.
OBJECTIVE
A significant proportion of hearing loss and deafness is caused by defects in the structure or function of cells within the organ of Corti. Identification of the molecular factors that regulate the development of this structure should provide valuable insights regarding inner ear formation and the signaling pathways that underlie congenital auditory deficits. In addition, targeted modulation of these same factors could be developed as therapies for hair cell regeneration.


RESULTS
Results from experiments using transgenic and mutant mice, as well as in-vitro techniques, have identified genes and signaling pathways that are required to either specify unique auditory cell types, such as hair cells or supporting cells, or to generate the highly ordered cellular pattern that is characteristic for the organ of Corti. In particular, the hedgehog and fibroblast growth factor signaling pathways modulate the formation of the progenitor cells that will give rise to the organ of Corti. SRY-box containing gene 2, a transcription factor that is required for the formation of the cochlear progenitor cell population, has paradoxically been shown to also act as an inhibitor of hair cell development. Finally, the motor protein myosin II regulates extension of the organ of Corti and the alignment of hair cells and supporting cells into ordered rows.


CONCLUSIONS
A better understanding of the signaling pathways that direct different aspects of cochlear development, such as specific of cell fates or cellular patterning, offers the potential to identify new pathways or molecules that could be targeted for therapeutic interventions.
Kelley
Matthew W
MW
Section on Developmental Neuroscience, National Institute on Deafness and other Communication Disorders, National Institutes of Health, Bethesda, Maryland, USA. kelleymt@nidcd.nih.gov
Driver
Elizabeth C
EC
Puligilla
Chandrakala
C
D000818:Animals; D051792:Basic Helix-Loop-Helix Proteins / Q000502:physiology; D002454:Cell Differentiation / Q000502:physiology; D005346:Fibroblast Growth Factors / Q000502:physiology; D053823:Hedgehog Proteins / Q000502:physiology; D051379:Mice; D008822:Mice, Transgenic; D024462:Myosin Type II / Q000502:physiology; D009925:Organ of Corti / Q000166:cytology* / Q000196:embryology*; D054975:Pallister-Hall Syndrome / Q000235:genetics; D055748:SOXB1 Transcription Factors / Q000502:physiology; D015398:Signal Transduction / Q000502:physiology
D051792:Basic Helix-Loop-Helix Proteins; D005346:Fibroblast Growth Factors; D053823:Hedgehog Proteins; D024462:Myosin Type II; D055748:SOXB1 Transcription Factors; C500943:Atoh1 protein, mouse; C527783:Sox2 protein, mouse