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NINDSNIMHNICHDNIDCDNEINIDCRNIANIAAANIDANHGRI NCCIHNIDDKNIEHSCCB

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Senior Investigator

Matthew Kelley, Ph.D.

Porter Neuroscience Research Center
Building 35 Room 2A-100
35 Convent Drive MSC 3729
Rockville MD 20850-3729
Office: (301) 435-8075
Lab: (301) 435-8075
Fax: (301) 435-4481
Kelleymt@nidcd.nih.gov

Dr. Kelley received his B.A. degree from Cornell University and his Ph.D. from the University of Virginia where he studied development and regeneration of mechanosensory hair cells with Jeffrey Corwin. After postdoctoral work at the University of Washington studying determination of cell fate in the vertebrate retina with Thomas Reh, he became a faculty member in Cell Biology at Georgetown University in 1996. In 2000 he moved to NIDCD as acting chief of the Section on Developmental Neuroscience. In 1999 he received the Burt Evans Young Investigator Award from the National Organization for Hearing Research. Dr. Kelley�s laboratory is studying the cellular, molecular and genetic interactions that play a role in the determination of cell fate and cellular patterning in the mammalian auditory system.



Current research in the laboratory is focused on the mechanisms that control the number of cells that will develop with each distinct phenotype. Previous results have demonstrated that the number of cells that will develop as sensory hair cells is regulated through inhibitory interactions between neighboring cells. These results suggest that the possible cell fates within the cochlea may be arranged in a hierarchy and that as the number of cells that become specified to develop as a single phenotype increases, these cells then begin to produce inhibitory signals that force the remaining cells to develop with alternate fates.

A second area of interest is the mechanisms that control overall cellular pattern with the cochlea. The cellular pattern of the mammalian cochlea is arranged in a gradient such that one type of sensory cell is located on one edge of the epithelium and a second type of sensory cell is located on the opposite edge. At both edges the sensory cells are arranged in distinct rows. The factors that specify the formation of this pattern are unknown; however, preliminary results suggest that the Wnt signaling pathway may play a role in the development of this pattern.

The overall goals of the Section on Developmental Neuroscience are to identify the molecular and cellular factors that play a role in the development of the sensory epithelium of the mammalian cochlea (the organ of Corti). The organ of Corti is comprised of at least 6 distinct cell types that are arranged in highly conserved mosaic. The generation of a specific number of each cell type and the arrangement of these cell types into a regular pattern are essential for the normal perception of sound; however, our understanding of the factors that play a role in the development of this structure is extremely limited.


Stereocilia bundles in the cochlea



                                          Stereocilia Bundles in the Organ of Corti
Recent work from our laboratory has begun to identify the molecular factors that play a role in regulating the uniform orientation of stereociliary bundles in the cochlea. Each stereociliary bundle has a "v" shape and the vertices for all bundles point in the same direction. The uniform orientation of these bundles is required for normal hearing, however the factors thar regulate this orientation are not known.

In two recent publications we have identified three factors that play a role in the generation of uniform orientation. Through analysis of mouse mutants we demonstrated that mutations in two genes, Vengl2 and Scrb1 both lead to orientation defects in the cochlea. In addition, using in vitro techniques we demonstrated that the Wnt signaling pathway also plays a role in stereciliary orientation.

Staff Image
  • Alain Dabdoub, Ph.D.
    Senior Investigator
    (301) 435-8074

  • Elizabeth Driver, Ph.D.
    Postdoctoral Fellow
    (301) 435-8074

  • Jose Gurrola, B.A.
    Predoctoral Fellow
    (301) 435-8074

  • Bonnie Jacques, B.S.
    Predoctoral Fellow
    (301) 435-8074

  • Jennifer Jones, B.Sc.
    Predoctoral Fellow
    (301) 435-8074

  • Mireille Montcouquiol, Ph.D.
    Research Fellow
    (301) 435-8074

  • Kala Puligilla, Ph.D.
    Postdoctoral Fellow
    (301) 435-8074

  • Chad Woods, M.S.
    Research Assistant
    (301) 435-8074

  • 1) Daboub, A., Donohue, M.J., Brennan, A., Wolf, V., Montcouquiol, M., Sasson, D.A., Hseih, J.-C., Rubin, J.S., Salinas, P.C. and Kelley, M.W. (2003)
  • Wnt Signaling Mediates Reorientation of Outer Hair Cell Stereociliary Bundles in the Mammalian Cochlea.
  • Development, 130, 2375-2384
  • 2) Montcouquiol, M., Rachel, R.A., Lanford, P.J., Copeland, N.G., Jenkins, N.A., and Kelley, M.W. (2003)
  • Identification of Vangl2 and Scrb1 as the first planar polarity genes in mammals.
  • Nature, 423, 173-176
  • 3) Mueller, K.L., Jacques, B.E. and Kelley, M.W. (2002)
  • FGF signaling regulates pillar cell development in the organ of Corti.
  • Journal of Neuroscience, 22, 9368-9377
  • 4) Rüsch, A., Ng, L., Goodyear, R., Oliver, D., Lisoukov, I., Vennström, B., Richardson, G., Kelley, M.W. and Forrest, D. (2001)
  • Retardation of cochlear maturation and impaired hair cell function caused by deletion of all known thyroid hormone receptors.
  • J. Neurosci., 21, 9792-9800
  • 5) Lanford PJ, Shailam R, Norton CR, Gridley T, Kelley MW. (2000)
  • Expression of Math1 and HES5 in the cochleae of wildtype and Jag2 mutant mice.
  • JARO , 1, 161-170
  • 6) Zhang N, Martin GV, Kelley MW, Gridley T. (2000)
  • A mutation in the Lunatic Fringe gene suppresses the effects of a Jagged2 mutation on inner hair cell development in the cochlea.
  • Currents in Biology , 10, 659-662
  • 8) Shailaim R, Lanford PJ, Dolinsky CM, Norton CR, Gridley T, Kelley MW. (1999)
  • Expression of proneural and neurogenic genes in the embryonic mammalian vestibular system.
  • Journal of Neurocytology , 28, 809-819
  • 9) Raz Y, Kelley, MW. (1999)
  • Retinoic acid signaling is necessary for the development of the organ of Corti.
  • Developmental Biology , 213, 180-193
  • 10) Lanford PJ, Lan Y, Jiang R, Lindsell C, Weinmaster G, Gridley T, Kelley MW. (1999)
  • Notch signaling pathway mediates hair cell development in mammalian cochlea. (with comment in News and Views)
  • Nature Genetics, 21, 289-292
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