Doris K. Wu, Ph.D.
Section on Sensory Cell Regeneration and Development
Laboratory of Molecular Biology
Porter Neuroscience Research Center
35A Convent Drive 1D-824
Bethesda, MD 20892-3729 for U.S. Postal Service
Bethesda, MD 20814 for other carriers (FedEx, UPS, etc.)
Telephone: (301) 402-4214 (office)
Morphogenesis of the mouse inner ear from embryonic day 10.75 to postnatal day 1. Mouse specimens from various ages were fixed, cleared, and the lumen of the inner ear was filled with a latex paint solution (Cantos et al. 2000; For a detailed description of this paint filling technique, see Morsli et al. 1998.) View larger image.
Humans and many animals rely on the inner ear, an intricate sensory organ, to hear and to maintain balance. Inner ear development is a complex process that is dependent on a cascade of molecular events, which occur in a precise temporal sequence. Any missteps in this process will most likely result in some degree of dysfunction affecting the abilities to hear and maintain balance.
My laboratory's goal is to identify the molecular mechanisms underlying the formation of this complex structure. Our focus is on identifying the tissues and signaling molecules that specify the three primary cell types (neural, sensory, and nonsensory) which make up the inner ear. We are also interested in the developmental mechanisms that dictate the spatial position and orientation of each of the inner ear components with respect to the overall body axes. To address these questions, we perform in ovo manipulations of chicken embryos and generate chicken and mouse models with genetic modifications.
- Timothy Chang, high school student (Send email)
- Youngrae Ji, Ph.D. (Send email)
- Tao Jiang, Ph.D. candidate (Send email)
- Andrew Lin, B.S. (Send email)
- Kaya Matson, B.S. (Send email)
- Michael Mulheisen, B.S., M.S. (Send email)
- Kazuya Ono, Ph.D. (Send email)
- Lok Sum Wong, Ph.D. (Send email)
- Sharda Yadav, Ph.D. (Send email)
- Evsen, L., Sugahara, S., Uchikawa, M., Kondoh H., Wu, D.K. Progression of neurogenesis in the inner ear requires inhibition of Sox2 transcription by neurogenin1 and neurod1. J Neurosci. 2013; vol33(9), pp 3879-90, 2013.
- Bok, J., Zenczak, C., Hwang, C.H., Wu, D. K. Auditory ganglion source of Sonic hedgehog regulates timing of cell cycle exit and differentiation of mammalian cochlear hair cells. PNAS, 2013, vol 110 no.34, pp.13869-13874.
- Bok, J., Raft, S., Kong, K., Koo, S.K., Dräger, U.C., Wu, D.K. Transient retinoic acid signaling confers anterior-posterior polarity to the inner ear. Proc Natl. Acad Sci. 108:161-166, 2011.
- Liang, J. K., Bok, J. and Wu, D. K. Distinct contributions from the hindbrain and mesenchyme to inner ear morphogenesis. Dev Bio. 337:324-34, 2010.
- Koo, S.K., Hill, J.K., Hwang C.H., Lin, Z.S., Millen, K.J., Wu, D.K. Lmx1a maintains proper neurogenic, sensory, and non-sensory domains in the mammalian inner ear. Dev Biol, 333:14-25, 2009.
- Chang, W., Lin, Z., Kulessa, H., Hebert, J., Hogan, B.L.M., and Wu, D. K. Bmp4 is essential for the formation of the vestibular apparatus that detects angular head movements. PLoS Genetics, 4:e1000050, 2008.
- Hwang, C. and Wu, D. K. Noggin heterozygous mice: an animal model for congenital conductive hearing loss in humans. Human Mol Genetics, 17:844-853, 2008.
- Bok, J., Dolson, D. K., Hill, P., Ruther, U., Epstein, D. J. and Wu, D. K. Opposing gradients of Gli repressor and activators mediate Shh signaling along the dorsoventral axis of the inner ear. Development, 134:1713-1722, 2007.
- Lin, Z., Cantos, R., Patente, M. and Wu, D. K. Gbx2 is required for the morphogenesis of the mouse inner ear: a downstream candidate of hindbrain signaling. Development, 132:2309-2318, 2005.
- Bok, J., Bronner-Fraser, M., and Wu, D. K. Role of the hindbrain in dorsoventral but not anteroposterior axial specification of the inner ear. Development,132:2115-2124, 2005.
- Chang, W., Brigande, J., Fekete, D. and Wu, D. K. The development of semicircular canals in the inner ear: role of FGFs in sensory cristae. Development, 131:4201-4211, 2004.
- Riccomagno, M., Martinu, L., Mulheisen, M., Wu, D. K., and Epstein, D. Specification of the mammalian cochlea is dependent on Sonic hedgehog. Genes & Dev, 16:2365-2378, 2002.
- Cantos, R., Cole, L., Acampora, D., Simeone, A. and Wu, D. K. Patterning of the mammalian cochlea. Proc Natl Acad Sci, 97:11707-11713, 2000.
- Morsli, H., Choo D., Ryan, A., Johnson, R. and Wu, D.K. Development of the mouse inner ear and origin of its sensory organs. J Neurosci, 18:3327-3335, 1998.
- Wu, D. K., Nunes, F. and Choo, D. Axial specification for sensory organs versus non-sensory structures of the chicken inner ear. Development, 125:11-20, 1998.