Note to users. If you're seeing this message, it means that your browser cannot find this page's style/presentation instructions -- or possibly that you are using a browser that does not support current Web standards. Find out more about why this message is appearing, and what you can do to make your experience of our site the best it can be.

Site Tools

  • AAAS
  • Subscribe
  • Feedback

Site Search

Search Advanced

Science 11 June 1999:
Vol. 284. no. 5421, pp. 1837 - 1841
DOI: 10.1126/science.284.5421.1837
Prev | Table of Contents | Next

Reports

Math1: An Essential Gene for the Generation of Inner Ear Hair Cells

Nessan A. Bermingham, 12 Bassem A. Hassan, 12 Steven D. Price, 7 Melissa A. Vollrath, 5 Nissim Ben-Arie, 2* Ruth Anne Eatock, 56 Hugo J. Bellen, 1245 Anna Lysakowski, 7 Huda Y. Zoghbi 12345dagger

The mammalian inner ear contains the cochlea and vestibular organs, which are responsible for hearing and balance, respectively. The epithelia of these sensory organs contain hair cells that function as mechanoreceptors to transduce sound and head motion. The molecular mechanisms underlying hair cell development and differentiation are poorly understood. Math1, a mouse homolog of the Drosophila proneural gene atonal, is expressed in inner ear sensory epithelia. Embryonic Math1-null mice failed to generate cochlear and vestibular hair cells. This gene is thus required for the genesis of hair cells.

1 Howard Hughes Medical Institute,
2 Department of Molecular and Human Genetics,
3 Department of Pediatrics,
4 Developmental Biology Program,
5 Division of Neuroscience,
6 Bobby R. Alford Department of Otorhinolaryngology and Communicative Sciences, Baylor College of Medicine, Houston, TX 77030, USA.
7 Department of Anatomy and Cell Biology, University of Illinois at Chicago, Chicago, IL 60612, USA.
*   Present address: Department of Cell and Animal Biology, Alexander Silberman Institute of Life Sciences, Hebrew University of Jerusalem, Givat-Ram, Jerusalem 91904, Israel.

dagger    To whom correspondence should be addressed. E-mail: hzoghbi{at}bcm.tmc.edu

Read the Full Text


THIS ARTICLE HAS BEEN CITED BY OTHER ARTICLES:
Inhibitory and excitatory subtypes of cochlear nucleus neurons are defined by distinct bHLH transcription factors, Ptf1a and Atoh1.
T. Fujiyama, M. Yamada, M. Terao, T. Terashima, H. Hioki, Y. U. Inoue, T. Inoue, N. Masuyama, K. Obata, Y. Yanagawa, et al. (2009)
Development 136, 2049-2058
   Abstract »    Full Text »    PDF »
Directed differentiation of mouse cochlear neural progenitors in vitro.
J. Lin, L. Feng, Y. Hamajima, M. Komori, T. C. Burns, S. Fukudome, J. Anderson, D. Wang, C. M. Verfaillie, and W. C. Low (2009)
Am J Physiol Cell Physiol 296, C441-C452
   Abstract »    Full Text »    PDF »
Cells of adult brain germinal zone have properties akin to hair cells and can be used to replace inner ear sensory cells after damage.
D. Wei, S. Levic, L. Nie, W.-q. Gao, C. Petit, E. G. Jones, and E. N. Yamoah (2008)
PNAS 105, 21000-21005
   Abstract »    Full Text »    PDF »
Sox2 signaling in prosensory domain specification and subsequent hair cell differentiation in the developing cochlea.
A. Dabdoub, C. Puligilla, J. M. Jones, B. Fritzsch, K. S. E. Cheah, L. H. Pevny, and M. W. Kelley (2008)
PNAS 105, 18396-18401
   Abstract »    Full Text »    PDF »
Eya1 gene dosage critically affects the development of sensory epithelia in the mammalian inner ear.
D. Zou, C. Erickson, E.-H. Kim, D. Jin, B. Fritzsch, and P.-X. Xu (2008)
Hum. Mol. Genet. 17, 3340-3356
   Abstract »    Full Text »    PDF »
Hedgehog Signaling Regulates Sensory Cell Formation and Auditory Function in Mice and Humans.
E. C. Driver, S. P. Pryor, P. Hill, J. Turner, U. Ruther, L. G. Biesecker, A. J. Griffith, and M. W. Kelley (2008)
J. Neurosci. 28, 7350-7358
   Abstract »    Full Text »    PDF »
Novel mutations in LHX3 are associated with hypopituitarism and sensorineural hearing loss.
A. Rajab, D. Kelberman, S. C.P. de Castro, H. Biebermann, H. Shaikh, K. Pearce, C. M. Hall, G. Shaikh, D. Gerrelli, A. Grueters, et al. (2008)
Hum. Mol. Genet. 17, 2150-2159
   Abstract »    Full Text »    PDF »
Fgf20 Is Required for Sensory Epithelial Specification in the Developing Cochlea.
T. Hayashi, C. A. Ray, and O. Bermingham-McDonogh (2008)
J. Neurosci. 28, 5991-5999
   Abstract »    Full Text »    PDF »
Barhl1 Regulatory Sequences Required for Cell-Specific Gene Expression and Autoregulation in the Inner Ear and Central Nervous System.
R. Chellappa, S. Li, S. Pauley, I. Jahan, K. Jin, and M. Xiang (2008)
Mol. Cell. Biol. 28, 1905-1914
   Abstract »    Full Text »    PDF »
Notch Signaling Regulates the Extent of Hair Cell Regeneration in the Zebrafish Lateral Line.
E. Y. Ma, E. W Rubel, and D. W. Raible (2008)
J. Neurosci. 28, 2261-2273
   Abstract »    Full Text »    PDF »
Architecture of the Mouse Utricle: Macular Organization and Hair Bundle Heights.
A. Li, J. Xue, and E. H. Peterson (2008)
J Neurophysiol 99, 718-733
   Abstract »    Full Text »    PDF »
Cross-regulation of Ngn1 and Math1 coordinates the production of neurons and sensory hair cells during inner ear development.
S. Raft, E. J. Koundakjian, H. Quinones, C. S. Jayasena, L. V. Goodrich, J. E. Johnson, N. Segil, and A. K. Groves (2007)
Development 134, 4405-4415
   Abstract »    Full Text »    PDF »
Inner ear hair cells produced in vitro by a mesenchymal-to-epithelial transition.
Z. Hu and J. T. Corwin (2007)
PNAS 104, 16675-16680
   Abstract »    Full Text »    PDF »
Notch signalling is needed to maintain, but not to initiate, the formation of prosensory patches in the chick inner ear.
N. Daudet, L. Ariza-McNaughton, and J. Lewis (2007)
Development 134, 2369-2378
   Abstract »    Full Text »    PDF »
Vlgr1 is required for proper stereocilia maturation of cochlear hair cells..
H. Yagi, H. Tokano, M. Maeda, T. Takabayashi, T. Nagano, H. Kiyama, S. Fujieda, K. Kitamura, and M. Sato (2007)
Genes Cells 12, 235-250
   Abstract »    Full Text »    PDF »
Distinct Population of Hair Cell Progenitors Can Be Isolated from the Postnatal Mouse Cochlea Using Side Population Analysis.
E. Savary, J. P. Hugnot, Y. Chassigneux, C. Travo, C. Duperray, T. Van De Water, and A. Zine (2007)
Stem Cells 25, 332-339
   Abstract »    Full Text »    PDF »
Zebrafish atoh1 genes: classic proneural activity in the inner ear and regulation by Fgf and Notch.
B. B. Millimaki, E. M. Sweet, M. S. Dhason, and B. B. Riley (2007)
Development 134, 295-305
   Abstract »    Full Text »    PDF »
The Transcription Factor six1 Inhibits Neuronal and Promotes Hair Cell Fate in the Developing Zebrafish (Danio rerio) Inner Ear.
O. Bricaud and A. Collazo (2006)
J. Neurosci. 26, 10438-10451
   Abstract »    Full Text »    PDF »
HATH1 Expression in Mucinous Cancers of the Colorectum and Related Lesions..
E. T. Park, H. K. Oh, J. R. Gum Jr., S. C. Crawley, S. Kakar, J. Engel, C. C. Leow, W.-Q. Gao, and Y. S. Kim (2006)
Clin. Cancer Res. 12, 5403-5410
   Abstract »    Full Text »    PDF »
COUP-TFI controls Notch regulation of hair cell and support cell differentiation.
L. S. Tang, H. M. Alger, and F. A. Pereira (2006)
Development 133, 3683-3693
   Abstract »    Full Text »    PDF »
A morphogenetic wave of p27Kip1 transcription directs cell cycle exit during organ of Corti development.
Y.-S. Lee, F. Liu, and N. Segil (2006)
Development 133, 2817-2826
   Abstract »    Full Text »    PDF »
Essential role of retinoblastoma protein in mammalian hair cell development and hearing.
C. Sage, M. Huang, M. A. Vollrath, M. C. Brown, P. W. Hinds, D. P. Corey, D. E. Vetter, and Z.-Y. Chen (2006)
PNAS 103, 7345-7350
   Abstract »    Full Text »    PDF »
Profile of Huda Y. Zoghbi.
R. Nuzzo (2006)
PNAS 103, 3017-3019
   Full Text »    PDF »
Inhibitors of Differentiation and DNA Binding (Ids) Regulate Math1 and Hair Cell Formation during the Development of the Organ of Corti.
J. M. Jones, M. Montcouquiol, A. Dabdoub, C. Woods, and M. W. Kelley (2006)
J. Neurosci. 26, 550-558
   Abstract »    Full Text »    PDF »
Gfi1 functions downstream of Math1 to control intestinal secretory cell subtype allocation and differentiation.
N. F. Shroyer, D. Wallis, K. J.T. Venken, H. J. Bellen, and H. Y. Zoghbi (2005)
Genes & Dev. 19, 2412-2417
   Abstract »    Full Text »    PDF »
The dosage of the neuroD2 transcription factor regulates amygdala development and emotional learning.
C.-H. Lin, S. Hansen, Z. Wang, D. R. Storm, S. J. Tapscott, and J. M. Olson (2005)
PNAS 102, 14877-14882
   Abstract »    Full Text »    PDF »
The retinoblastoma gene pathway regulates the postmitotic state of hair cells of the mouse inner ear.
J. Mantela, Z. Jiang, J. Ylikoski, B. Fritzsch, E. Zacksenhaus, and U. Pirvola (2005)
Development 132, 2377-2388
   Abstract »    Full Text »    PDF »
Commissural neuron identity is specified by a homeodomain protein, Mbh1, that is directly downstream of Math1.
R. Saba, J. E. Johnson, and T. Saito (2005)
Development 132, 2147-2155
   Abstract »    Full Text »    PDF »
Clonal analysis of the relationships between mechanosensory cells and the neurons that innervate them in the chicken ear.
T. Satoh and D. M. Fekete (2005)
Development 132, 1687-1697
   Abstract »    Full Text »    PDF »
Comparative Morphology of Rodent Vestibular Periphery. I. Saccular and Utricular Maculae.
S. S. Desai, C. Zeh, and A. Lysakowski (2005)
J Neurophysiol 93, 251-266
   Abstract »    Full Text »    PDF »
Gfi/Pag-3/Senseless Zinc Finger Proteins: a Unifying Theme?.
H. Jafar-Nejad and H. J. Bellen (2004)
Mol. Cell. Biol. 24, 8803-8812
   Full Text »    PDF »
Molecular profiling reveals synaptic release machinery in Merkel cells.
H. Haeberle, M. Fujiwara, J. Chuang, M. M. Medina, M. V. Panditrao, S. Bechstedt, J. Howard, and E. A. Lumpkin (2004)
PNAS 101, 14503-14508
   Abstract »    Full Text »    PDF »
The developmental genetics of auditory hair cells.
R. D. Hawkins and M. Lovett (2004)
Hum. Mol. Genet. 13, R289-R296
   Abstract »    Full Text »    PDF »
Transcription profiling of inner ears from Pou4f3ddl/ddl identifies Gfi1 as a target of the Pou4f3 deafness gene.
R. Hertzano, M. Montcouquiol, S. Rashi-Elkeles, R. Elkon, R. Yucel, W. N. Frankel, G. Rechavi, T. Moroy, T. B. Friedman, M. W. Kelley, et al. (2004)
Hum. Mol. Genet. 13, 2143-2153
   Abstract »    Full Text »    PDF »
Hath1, Down-Regulated in Colon Adenocarcinomas, Inhibits Proliferation and Tumorigenesis of Colon Cancer Cells.
C. C. Leow, M. S. Romero, S. Ross, P. Polakis, and W.-Q. Gao (2004)
Cancer Res. 64, 6050-6057
   Abstract »    Full Text »    PDF »
From placode to polarization: new tunes in inner ear development.
K. F. Barald and M. W. Kelley (2004)
Development 131, 4119-4130
   Abstract »    Full Text »    PDF »
Evolution of neural precursor selection: functional divergence of proneural proteins.
X.-J. Quan, T. Denayer, J. Yan, H. Jafar-Nejad, A. Philippi, O. Lichtarge, K. Vleminckx, and B. A. Hassan (2004)
Development 131, 1679-1689
   Abstract »    Full Text »    PDF »
Suppression of neural fate and control of inner ear morphogenesis by Tbx1.
S. Raft, S. Nowotschin, J. Liao, and B. E. Morrow (2004)
Development 131, 1801-1812
   Abstract »    Full Text »    PDF »
Barhl1 Regulates Migration and Survival of Cerebellar Granule Cells by Controlling Expression of the Neurotrophin-3 Gene.
S. Li, F. Qiu, A. Xu, S. M. Price, and M. Xiang (2004)
J. Neurosci. 24, 3104-3114
   Abstract »    Full Text »    PDF »
Distinct domains within Mash1 and Math1 are required for function in neuronal differentiation versus neuronal cell-type specification.
Y. Nakada, T. L. Hunsaker, R. M. Henke, and J. E. Johnson (2004)
Development 131, 1319-1330
   Abstract »    Full Text »    PDF »
Analysis of Cerebellar Development in math1 Null Embryos and Chimeras.
P. Jensen, R. Smeyne, and D. Goldowitz (2004)
J. Neurosci. 24, 2202-2211
   Abstract »    Full Text »    PDF »
Math1 controls cerebellar granule cell differentiation by regulating multiple components of the Notch signaling pathway.
R. Gazit, V. Krizhanovsky, and N. Ben-Arie (2004)
Development 131, 903-913
   Abstract »    Full Text »    PDF »
From The Cover: Generation of hair cells by stepwise differentiation of embryonic stem cells.
H. Li, G. Roblin, H. Liu, and S. Heller (2003)
PNAS 100, 13495-13500
   Abstract »    Full Text »    PDF »
Planar and Vertical Signals Control Cellular Differentiation and Patterning in the Mammalian Cochlea.
M. Montcouquiol and M. W. Kelley (2003)
J. Neurosci. 23, 9469-9478
   Abstract »    Full Text »    PDF »
Drosophila spalt/spalt-related mutants exhibit Townes-Brocks' syndrome phenotypes.
P. D. S. Dong, S. V. Todi, D. F. Eberl, and G. Boekhoff-Falk (2003)
PNAS 100, 10293-10298
   Abstract »    Full Text »    PDF »
Gene expression differences in quiescent versus regenerating hair cells of avian sensory epithelia: implications for human hearing and balance disorders.
R. D. Hawkins, S. Bashiardes, C. A. Helms, L. Hu, N. L. Saccone, M. E. Warchol, and M. Lovett (2003)
Hum. Mol. Genet. 12, 1261-1272
   Abstract »    Full Text »    PDF »
Math1 Gene Transfer Generates New Cochlear Hair Cells in Mature Guinea Pigs In Vivo.
K. Kawamoto, S.-I. Ishimoto, R. Minoda, D. E. Brough, and Y. Raphael (2003)
J. Neurosci. 23, 4395-4400
   Abstract »    Full Text »    PDF »
Zic1 represses Math1 expression via interactions with the Math1 enhancer and modulation of Math1 autoregulation.
P. J. Ebert, J. R. Timmer, Y. Nakada, A. W. Helms, P. B. Parab, Y. Liu, T. L. Hunsaker, and J. E. Johnson (2003)
Development 130, 1949-1959
   Abstract »    Full Text »    PDF »
Hearing loss caused by progressive degeneration of cochlear hair cells in mice deficient for the Barhl1 homeobox gene.
S. Li, S. M. Price, H. Cahill, D. K. Ryugo, M. M. Shen, and M. Xiang (2003)
Development 129, 3523-3532
   Abstract »    Full Text »    PDF »
The role of Math1 in inner ear development: Uncoupling the establishment of the sensory primordium from hair cell fate determination.
P. Chen, J. E. Johnson, H. Y. Zoghbi, and N. Segil (2003)
Development 129, 2495-2505
   Abstract »    Full Text »    PDF »
Distal-less and homothorax regulate multiple targets to pattern the Drosophila antenna.
P. D. S. Dong, J. S. Dicks, and G. Panganiban (2003)
Development 129, 1967-1974
   Abstract »    Full Text »    PDF »
The zinc finger transcription factor Gfi1, implicated in lymphomagenesis, is required for inner ear hair cell differentiation and survival.
D. Wallis, M. Hamblen, Y. Zhou, K. J. T. Venken, A. Schumacher, H. L. Grimes, H. Y. Zoghbi, S. H. Orkin, and H. J. Bellen (2003)
Development 130, 221-232
   Abstract »    Full Text »    PDF »
Gene expression profile of human endothelial cells exposed to sustained fluid shear stress.
S. M. Wasserman, F. Mehraban, L. G. Komuves, R.-B. Yang, J. E. Tomlinson, Y. Zhang, F. Spriggs, and J. N. Topper (2002)
Physiol Genomics 12, 13-23
   Abstract »    Full Text »    PDF »
Energy Integration Describes Sound-Intensity Coding in an Insect Auditory System.
T. Gollisch, H. Schutze, J. Benda, and A. V. M. Herz (2002)
J. Neurosci. 22, 10434-10448
   Abstract »    Full Text »    PDF »
Cochlear pathology, sensory cell death and regeneration.
Y. Raphael (2002)
Br. Med. Bull. 63, 25-38
   Abstract »    Full Text »    PDF »
Sensory organ development in the inner ear: molecular and cellular mechanisms.
J. Bryant, R. J Goodyear, and G. P Richardson (2002)
Br. Med. Bull. 63, 39-57
   Abstract »    Full Text »    PDF »
Dissection of the Cellular and Molecular Events that Position Cerebellar Purkinje Cells: A Study of the math1 Null-Mutant Mouse.
P. Jensen, H. Y. Zoghbi, and D. Goldowitz (2002)
J. Neurosci. 22, 8110-8116
   Abstract »    Full Text »    PDF »
Transcript Profiling of Functionally Related Groups of Genes During Conditional Differentiation of a Mammalian Cochlear Hair Cell Line.
M. N. Rivolta, A. Halsall, C. M. Johnson, M. A. Tones, and M. C. Holley (2002)
Genome Res. 12, 1091-1099
   Abstract »    Full Text »    PDF »
Studies of mechanosensation using the fly.
A. P. Jarman (2002)
Hum. Mol. Genet. 11, 1215-1218
   Abstract »    Full Text »    PDF »
Divergent functions of the proneural genes Mash1 and Ngn2 in the specification of neuronal subtype identity.
C. M. Parras, C. Schuurmans, R. Scardigli, J. Kim, D. J. Anderson, and F. Guillemot (2002)
Genes & Dev. 16, 324-338
   Abstract »    Full Text »    PDF »
Developmental functions of the Distal-less/Dlx homeobox genes.
G. Panganiban and J. L. R. Rubenstein (2002)
Development 129, 4371-4386
   Abstract »    Full Text »    PDF »
A specific promoter of the sensory cells of the inner ear defined by transgenesis.
B. Boeda, D. Weil, and C. Petit (2001)
Hum. Mol. Genet. 10, 1581-1589
   Abstract »    Full Text »    PDF »
Hes1 and Hes5 Activities Are Required for the Normal Development of the Hair Cells in the Mammalian Inner Ear.
A. Zine, A. Aubert, J. Qiu, S. Therianos, F. Guillemot, R. Kageyama, and F. de Ribaupierre (2001)
J. Neurosci. 21, 4712-4720
   Abstract »    Full Text »    PDF »
Math5 is required for retinal ganglion cell and optic nerve formation.
N. L. Brown, S. Patel, J. Brzezinski, and T. Glaser (2001)
Development 128, 2497-2508
   Abstract »    Full Text »    PDF »
NeuroD-null mice are deaf due to a severe loss of the inner ear sensory neurons during development.
W. Kim, B Fritzsch, A Serls, L. Bakel, E. Huang, L. Reichardt, D. Barth, and J. Lee (2001)
Development 128, 417-426
   Abstract »    PDF »
Essential role of BETA2/NeuroD1 in development of the vestibular and auditory systems.
M. Liu, F. A. Pereira, S. D. Price, M.-j. Chu, C. Shope, D. Himes, R. A. Eatock, W. E. Brownell, A. Lysakowski, and M.-J. Tsai (2000)
Genes & Dev. 14, 2839-2854
   Abstract »    Full Text »
Notch signaling in the development of the inner ear: Lessons from Drosophila.
M. Eddison, I. Le Roux, and J. Lewis (2000)
PNAS 97, 11692-11699
   Abstract »    Full Text »    PDF »
Cellular studies of auditory hair cell regeneration in birds.
J. S. Stone and E. W Rubel (2000)
PNAS 97, 11714-11721
   Abstract »    Full Text »    PDF »
Hair cell recovery in mitotically blocked cultures of the bullfrog saccule.
R. A. Baird, M. D. Burton, D. S. Fashena, and R. A. Naeger (2000)
PNAS 97, 11722-11729
   Abstract »    Full Text »    PDF »
Two mechanisms for transducer adaptation in vertebrate hair cells.
J. R. Holt and D. P. Corey (2000)
PNAS 97, 11730-11735
   Abstract »    Full Text »    PDF »
Notch Signaling and the Emergence of Auditory Hair Cells.
J. Weir, M. N. Rivolta, and M. C. Holley (2000)
Arch Otolaryngol Head Neck Surg 126, 1244-1248
   Abstract »    Full Text »    PDF »
Doing the MATH: is the mouse a good model for fly development?.
B. A. Hassan and H. J. Bellen (2000)
Genes & Dev. 14, 1852-1865
   Full Text »
A Drosophila Mechanosensory Transduction Channel.
R. G. Walker, A. T. Willingham, and C. S. Zuker (2000)
Science 287, 2229-2234
   Abstract »    Full Text »
Helix-Loop-Helix Proteins: Regulators of Transcription in Eucaryotic Organisms.
M. E. Massari and C. Murre (2000)
Mol. Cell. Biol. 20, 429-440
   Full Text »
Hes1 is a negative regulator of inner ear hair cell differentiation.
J. Zheng, J Shou, F Guillemot, R Kageyama, and W. Gao (2000)
Development 127, 4551-4560
   Abstract »    PDF »
Functional conservation of atonal and Math1 in the CNS and PNS.
N Ben-Arie, B. Hassan, N. Bermingham, D. Malicki, D Armstrong, M Matzuk, H. Bellen, and H. Zoghbi (2000)
Development 127, 1039-1048
   Abstract »    PDF »
Autoregulation and multiple enhancers control Math1 expression in the developing nervous system.
A. Helms, A. Abney, N Ben-Arie, H. Zoghbi, and J. Johnson (2000)
Development 127, 1185-1196
   Abstract »    PDF »
Visualization of alpha 9 acetylcholine receptor expression in hair cells of transgenic mice containing a modified bacterial artificial chromosome.
J. Zuo, J. Treadaway, T. W. Buckner, and B. Fritzsch (1999)
PNAS 96, 14100-14105
   Abstract »    Full Text »    PDF »
The deltaA gene of zebrafish mediates lateral inhibition of hair cells in the inner ear and is regulated by pax2.1.
B. Riley, M Chiang, L Farmer, and R Heck (1999)
Development 126, 5669-5678
   Abstract »    PDF »


To Advertise     Find Products

Science. ISSN 0036-8075 (print), 1095-9203 (online)