Abstract
The early development of the hair cell involves a cell fate commitment step in which sensory epithelial cells chose either the hair cell or supporting cell lineage. This is followed by differentiation, in which morphological and functional characteristics of the hair cell are acquired. The development of mechanosensory neurons in C. elegans, neurons that appear similar to the ancestors of hair cells, is controlled by the POU-domain transcription factor Unc-86. We have explored the role of a mammalian homologue, Brn-3.1, in hair cell development. Brn-3.1 is expressed selectively in hair cell precursors immediately following commitment to the hair cell lineage, and is expressed in hair cells throughout life. Deletion of the Brn-3.1 gene prevents the differentiation of the normal anatomical or functional features of hair cells, resulting in deafness and vestibular dysfunction. Mutation of the gene encoding Brn-3.1 in humans produces late-onset deafness. Brn-3.1 is thus highly specific to hair cells, and is required both for their normal development and survival.
This is a preview of subscription content, log in via an institution to check access.
Access this chapter
Tax calculation will be finalised at checkout
Purchases are for personal use only
Preview
Unable to display preview. Download preview PDF.
References
Bermingham N.A., Hassan B.A., Price S.D., Vollrath M.A., Ben-Arie N., Eatock R.A., Bellen H.J., Lysakowski A., and Zoghbi H.Y. Mathl: an essential gene for the generation of inner ear hair cells. Science 284: 1837–1841, 1999.
Brownlees J., Gough G., Thomas S., Watts P., Cohen J., Coffin R., and Latchman D.S. Distinct responses of the herpes simplex virus and varicella zoster virus immediate early promoters to the cellular transcription factors Brn-3a and Brn-3b. Intl. J. Biochem. Cell Biol. 31: 451–461,1999.
Budhram-Mahadeo V., Parker M., and Latchman D.S. POU transcription factors Brn-3a and Brn-3b interact with the estrogen receptor and differentially regulate transcriptional activity via an estrogen response element. Molec. Cell Biol. 18: 1029–1041,1998.
Erkman L., McEvilly R.J., Luo L., Ryan A.E., Hoosmand F., O’Connell S.M., Keithley E.M., Rappaport D.H., Ryan A.F., and Rosenfeld M.G. Requirement for Brn-3.1 and Brn-3.2 in auditory and visual system development. Nature 381: 603–606, 1996.
Gay R.D., Dawson S.J., Murphy W.J., Russell S.W., and Latchman D.S. Activation of the iNOS gene promoter by Brn-3 POU family transcription factors is dependent upon the octamer motif in the promoter. Biochim. Biophys. Acta. 1443: 315–322, 1998.
Gu G., Caldwell G.A., and Chalfie M. Genetic interactions affecting touch sensitivity in Caenorhabditis elegans. PNAS 93: 6577–66582, 1996.
Keithley E.M., Erkman L., Bennett T., Luo L., and Ryan A.F. Effects of a hair cell transcription factor, Brn-3.1, deletion on homozygous and heterozygous mouse cochleas in adulthood and aging. Hearing Res. In press, 1999.
Lakin N.D., Morris P.J., Theil T., Sato T.N., Mèorèoy T., Wilson M.C., and Latchman D.S. Regulation of neurite outgrowth and SNAP-25 gene expression by the Brn-3a transcription factor. J. Biol. Chem. 270: 15858–15863,1995.
Lanford P.J., Lan Y., Jiang R., Lindsell C., Weinmaster G., Gridley T., and Kelley M.W. Notch signalling pathway mediates hair cell development in mammalian cochlea. Nature Genet. 21: 289–292,1999.
Li S., Crenshaw E.B., Rawson E.J., Simmons D.M., Swanson L.W., and Rosenfeld M.G. Dwarf locus mutants lacking three pituitary cell types result from mutations in the POU-domain gene Pit-1. Nature 347: 528–533,1990.
Milton N.G., Bessis A., Changeux J.P., and Latchman D.S. The neuronal nicotinic acetylcholine receptor alpha 2 subunit gene promoter is activated by the Brn-3b POU family transcription factor and not by Brn-3a or Brn-3c. J. Biol. Chem. 270: 15143–15147,1995.
Milton N.G., Bessis A., Changeux J.P., Latchman D.S. Differential regulation of neuronal nicotinic acetylcholine receptor subunit gene promoters by Brn-3 POU family transcription factors. Biochem. J. 317: 419–423, 1996.
Morris P.J., Lakin N.D., Dawson S.J., Ryabinin A.E., Kilimann M.W., Wilson M.C., and Latchman D.S. Differential regulation of genes encoding synaptic proteins by members of the Brn-3 subfamily of POU transcription factors. Molec. Brain Res. 43: 279–285, 1996.
Ruben R.J. Development of the inner ear of the mouse: a radioautographic study of terminal mitoses. Acta Otolaryngol: Suppl 220: 1–44, 1967.
Rudnicki M.A., Schnegelsberg P.N., Stead R.H., Braun T., Arnold H.H., and Jaenisch R. MyoD or Myf-5 is required for the formation of skeletal muscle. Cell 75: 1351–1359, 1993.
Ryan A.F. Transcription factors and the control of inner ear development. Sem. Cell Devel. Biol. 8: 249–256,1997.
Ryan A.F., Luo L., McEvilly R., Erkman L., and Rosenfeld M.G. A transcription factor specific for mammalian hair cells is expressed throughout life. Abstr. ARO 19: 575, 1996.
Ryan A.F., Simmons D.M., and Crenshaw E.B. Gene expression in normal and abnormal inner ears. Ann. NY Acad. Sci. 630: 129–132, 1991.
Ryan A.K., and Rosenfeld M.G. POU domain family values: flexibility, partnerships and developmental codes. Genes Devel. 11: 1207–1225,1997.
Smith M.D., Ensor E.A., Coffin R.S., Boxer L.M., and Latchman D.S. Bc1–2 transcription from the proximal P2 promoter is activated in neuronal cells by the Brn-3a POU family transcription factor. J. Biol. Chem. 273: 16715–16722, 1998.
Smith M.D., Morris P.J., Dawson S.J., Schwartz M.L., Schlaepfer W.W., and Latchman D.S. Coordinate induction of the three neurofilament genes by the Brn-3a transcription factor. J. Biol. Chem. 272: 21325–21333,1997.
Tavernarakis N., and Driscoll M. Molecular modeling of mechanotransduction in the nematode Caenorhabditis elegans. Ann. Rev. Physiol. 59: 659–689,1997.
Vahava O., Morell R., Lynch E.D., Weiss S., Kagan M.E., Ahituv N., Morrow J.E., Lee M.K., Skvorak A.B., Morton C.C., Blumenfeld A., Frydman M., Friedman T.B., King M.C., and Avraham K.B. Mutation in transcription factor POU4F3 associated with inherited progressive hearing loss in humans. Science 279: 1950–1954,1998.
Xiang M., Gan L., Li D., Chen Z.Y., Zhou L., O’Malley B.W., Klein W., and Nathans J. Essential role of POU-domain factor Brn-3c in auditory and vestibular hair cell development. PNAS 94: 9445–9450, 1997.
Xiang M., Gao W.Q., Hasson T., and Shin J.J. Requirement for Brn-3c in maturation and survival, but not in fate determination of inner ear hair cells. Development 125: 3935–3946, 1998.
Author information
Authors and Affiliations
Editor information
Editors and Affiliations
Rights and permissions
Copyright information
© 2000 Kluwer Academic/Plenum Publishers, New York
About this chapter
Cite this chapter
Ryan, A.F. (2000). Role of the POU-Domain Transcription Factor Brn-3.1 in Hair Cell Development. In: Lim, D.J. (eds) Cell and Molecular Biology of the Ear. Springer, Boston, MA. https://doi.org/10.1007/978-1-4615-4223-0_8
Download citation
DOI: https://doi.org/10.1007/978-1-4615-4223-0_8
Publisher Name: Springer, Boston, MA
Print ISBN: 978-1-4613-6896-0
Online ISBN: 978-1-4615-4223-0
eBook Packages: Springer Book Archive