Browse Faculty A-Z

Neil Segil

Professor of Research
Department of Regenerative Medicine and Stem Cell Biology
Keck School of Medicine of the University of Southern California

Neil  Segil

Research Topics

  • embryonic development of the inner ear
  • sensory hair cell regeneration
  • cell cycle control during development
  • cellular homeostasis ? DNA repair
  • stem/progenitor cell biology

Research Images

Chen, P., Zindy, F., Abdala, C., Liu, F., Li, X., Roussel, M.F., and Segil, N. (2003). Progressive hearing loss in mice lacking the cyclin-dependent kinase inhibitor Ink4d. Nature Cell Biology 5:422-426
Chen, P., Zindy, F., Abdala, C., Liu, F., Li, X., Roussel, M.F., and Segil, N. (2003). Progressive hearing loss in mice lacking the cyclin-dependent kinase inhibitor Ink4d. Nature Cell Biology 5:422-426
Doetzlhofer, A., White, P.M., Johnson, J.E., Segil, N., and Groves, A.K. (2004). In vitro growth and differentiation of mammalian sensory hair cell progenitors: a requirement for EGF and periotic mesenchyme.  Developmental Biology, 272:432–447.
Doetzlhofer, A., White, P.M., Johnson, J.E., Segil, N., and Groves, A.K. (2004). In vitro growth and differentiation of mammalian sensory hair cell progenitors: a requirement for EGF and periotic mesenchyme. Developmental Biology, 272:432–447.
White, P.M., Doetzlhofer, A., Lee, Y.-S., Groves, A.K., and Segil, N. (2006) Mammalian cochlear supporting cells can divide and trans-differentiate into hair cells.  Nature 441:984-987.
White, P.M., Doetzlhofer, A., Lee, Y.-S., Groves, A.K., and Segil, N. (2006) Mammalian cochlear supporting cells can divide and trans-differentiate into hair cells. Nature 441:984-987.

Research Overview

1) Embryonic development of the inner ear:
Coordinating cell proliferation, growth and differentiation is crucial for the development of animal form. This project investigates the biochemical machinery responsible for this coordination. We are investigating the role and regulation of cyclin-dependent kinase inhibitors (CKIs) in the formation of the prosensory domains in the inner ear, the cells that give rise to the organ of Corti and the vestibular sensory areas. In addition, we are studying the biochemical basis for hair cell and supporting cell differentiation within the developing mosaic of the sensory epithelia, and its relation to the stability of the differentiated state. In particular, we are studying the epigenetic regulation of transcription associated with Notch-dependent signaling within this system.

2) Sensory cell regeneration - cellular reprogramming - postnatal changes in progenitors/stem cells of the inner ear: (Grad student project available in neurophysiological characterization following cellular reprogramming, as part of new Regenerative Medicine Initiative).
We are engaged in identifying and manipulating sensory progenitors/stem cells as potential targets for therapeutic approaches to hearing loss through regeneration. We have developed tools, in the form of cell-type specific markers and purification techniques, as well as cell culture methods for studying the behavior of sensory cell progenitors. We are currently using these tools to characterize the lineage and regenerative potential of specific cell populations within the postnatal inner ear.
A new project involves direct reprogramming of differentiated cells to the sensory lineage.

3) Homeostasis and repair in the aging nervous system: the cell cycle, DNA damage and DNA repair:
The goal of this project is to understand the basis for the lifelong homeostatic maintenance of permanently postmitotic cells in the nervous system, including the inner ear. Sensory hair cells, like most neurons, stop dividing either in the embryo or shortly after birth. If lost due to environmental stress (loud noise, chemotherapy agents, antibiotics, aging) these cells do not regenerate. This means that lifelong cell renewal/repair must occur on an ongoing basis in the absence of cell replacement and in the presence of strong control over cell division. These factors are associated with a heightened sensitivity to physiological/environmental stress. Our focus is on how the cell cycle machinery in hair cells contributes to their sensitivity to stress, and how these pathways interact with other homeostatic pathways, such as those involved in DNA damage and repair. Currently, we are studying mouse models of the human DNA repair disorder, Cockayne Syndrome, which is associated with aspects of premature aging, and, as our current research indicates, sensory-neural hearing loss.


Contact Information

Mailing Address Broad/CIRM Center for
Regenerative Medicine and Stem Cell Research
Keck School of Medicine of
University of Southern California
1425 San Pablo Street -- BCC211
Los Angeles, CA 90033
Office Location BCC 506
Office Phone (323) 442-1549
Lab Location Broad/CIRM - BCC
Lab Phone
Fax
Office Location BCC 506

Websites

Education

  • B.A., Hampshire College, Amherst, MA, 1975.
  • Ph.D., Columbia University, New York, NY, 1989.

Selected Publications

View a complete PubMed searchView a complete Google Scholar search
  • Doetzlhofer, A., Basch, M. Gessler, M., Groves, A. K., and Segil, N. (2009).  Hey2 regulation by FGF provides a Notch-independent mechanism for maintaining pillar cell fate in the organ of Corti.  Developmental Cell 16: 58-69. PubMed
  • Jayasena CS, Ohyama T, Segil N, Groves AK. (2008) Notch signaling augments the canonical Wnt pathway to specify the size of the otic placode. Development. 135(13):2251-61. PubMed Link
  • Raft S, Koundakjian EJ, Quinones H, Jayasena CS, Goodrich LV, Johnson JE, Segil N, Groves AK. (2007) Cross-regulation of Ngn1 and Math1 coordinates the production of neurons and sensory hair cells during inner ear development. Development. 134(24):4405-15. PubMed
  • White, P.M., Doetzlhofer, A., Lee, Y.-S., Groves, A.K., and Segil, N. (2006) Mammalian cochlear supporting cells can divide and trans-differentiate into hair cells.  Nature  441:984-987. PubMed
  • Lee, Y.-S. Liu, F., and Segil, N (2006). Transcriptional Regulation of p27Kip1 Directs a Morphogenetic Wave of Cell Cycle Exit in the Developing Organ of Corti. Development 133:2817-26. PubMed
  • Laine H, Doetzlhofer A, Mantela J, Ylikoski J, Laiho M, Roussel MF, Segil N, Pirvola U. (2007) p19(Ink4d) and p21(Cip1) collaborate to maintain the postmitotic state of auditory hair cells, their codeletion leading to DNA damage and p53-mediated apoptosis. J Neurosci. 27(6):1434-44. PubMed
  • Chen, P., Zindy, F., Abdala, C., Liu, F., Li, X., Roussel, M.F., and Segil, N. (2003). Progressive hearing loss in mice lacking the cyclin-dependent kinase inhibitor Ink4d. Nature Cell Biology 5:422-426 PubMed
  • Chen P, Segil N. (1999) p27Kip1 links cell proliferation to morphogenesis in the developing organ of Corti. Development 126:1581-1590. PubMed
  • Segil N, Guermah M, Hoffmann A, Roeder RG, Heintz N. (1996) Mitotic regulation of TFIID: Inhibition of activator-dependent transcription and changes in sub-cellular localization. Genes and Development 10:2389-2400. PubMed
  • Segil N, Roberts SB, Heintz N. (1991) Mitotic phosphorylation of the Oct-1 POU-homeodomain and the regulation of Oct-1 DNA binding activity. Science 254:1814-1816. PubMed