The John and Donna Krenicki Directorship of Integrative Neuroscience
My laboratory is interested in the molecular basis of inner ear development, including morphogenesis, cell fate specification, axon guidance and sensory cell differentiation. The vertebrate inner ear houses the sensory organs for hearing and balance. Sound reaches these sensory cells through a series of conductive elements that comprise the outer and middle ears. Components of the inner ear include a fluid-filled epithelial sac and resident neuronal ganglion cells, all surrounded by loose mesenchyme and bone. These tissues originate on the side of the head, either from the ectodermally-derived otic placode, the neural crest, the presomitic mesoderm or the endoderm. Because of these varied embryonic origins, ear malformations often occur in the context of developmental problems in other organs or tissues, leading to syndromic forms of deafness. Over 400 forms of syndromic deafness have been characterized in humans. In other cases, deafness is the only known defect, and in those cases the responsible genes are often associated with some specialized function of inner ear sensory cells. In addition to hearing loss, genetic defects in ear formation or function can also lead to balance disorders. At present, there are hundreds of genes expressed in the embryonic ear that need to be functionally analyzed for their role in ear development and function.
Our lab primarily uses chicken, zebrafish and mouse as animal models in our research. We have a specific interest in studying the Wnt signaling pathway and the roles of microRNAs, a small class of non-coding RNAs that serve to regulate gene expression. Ongoing collaborations with other research labs inform our choice of candidate genes to explore and manipulate. We use gene transfer techniques including infection with viral vectors or electroporation of plasmid DNA (in chicken embryos) and direct injection into one-celled embryos (in zebrafish) to manipulate the levels of candidate molecules during development. Both overexpression and knockdown approaches can be informative in revealing the normal function of a candidate gene. Our hope is that the outcome of our research endeavors will lead to the design of new therapeutic treatments for deafness and balance disorders. For example, we have designed a study to use viral gene transfer to deliver microRNAs into the drug-damaged mouse cochlea to attempt to induce hair cell regeneration and rescue hearing loss.
Current Lab Personnel:
Research Assistant and Lab Manager: Deb Biesemeier
Postdoctoral Fellow: Vidhya Munnamalai
Graduate Students: Katie Scott, Ankita Thawani, Kristina Kirshner
Undergraduate Students: Karen Song, Syndey Tola, Alex Bikker, Rachel Adduci
The movie shows how the embryonic chicken inner ear develops from a simple round vesicle into the complex labyrinth that includes semicircular canals on top and the sickle-shaped cochlear duct on the bottom. The sequence begins on the third day after the egg is laid and ends on the 16th day. The chick hatches during the 21st day. The ears were fixed, dehydrated, cleared, and injected with white latex paint; digital images were taken through a dissection microscope and morphing software was applied to visualize structural changes over time. The images and movie are courtesy of J.P. Bissonnette and Laurie Iten, respectively.
B.S., Biological Sciences, summa cum laude, University of Vermont, 1979
Ph.D., Anatomy, Harvard University, 1984
Postdoctoral Fellow, MRC Cell Biophysics Unit and Ludwig Institute for Cancer Research, London, England
Postdoctoral Fellow, Department of Genetics, Harvard Medical School
Basil O'Connor Scholar, March of Dimes Birth Defects Foundation (1993-1996)
Clare Booth Luce Professorship, Henry Luce Foundation (1993-1998)
Marcus Singer Award, Midwest Regional Developmental Biology Meeting (2001)
University Faculty Scholar, Purdue University (2005-2010)
AAAS Fellow (2009)
J. Alfred and Martha Chiscon Undergraduate Teaching Award, Department of Biological Sciences, Purdue University (2011)
Faculty of 1000 (2011)
Leadership Award, College of Science, Purdue University (2011, 2015)
NIH RO1DC02756, Development studies of the inner ear, 03/01/2009-02/28/2014
- Developmental Biology
- Developmental Neurobiology
- Journal of Neuroscience
- Developmental Dynamics
Other Professional Activities
- Director, Integrative Neuroscience Center, Purdue University
- Director, Purdue Integrative Neuroscience Training Group, PULSe Graduate Program
- Member, Society for Neuroscience
- Member, Society for Developmental Biology
- Member, Association for Research in Otolaryngology
- Member, American Association for the Advancement of Science
- Member, Purdue Cancer Center
Recent Faculty Presentations
- "Specification of Sensory Fates in the Vertebrate Inner Ear", Symposium Session on Placode Development, American Association of Anatomists, FASEB Meeting, Washington, D.C., 11 April, 2011.
- "What zebrafish teaches us about microRNAs", Keynote speaker, 2nd Annual Tel Aviv University microRNA Consortium Conference, Tel Aviv, Israel, January 2010.
- "Development of the Vertebrate Inner Ear: Multiple Roles for Wnt signaling", Invited speaker for the Research Conference in Biomedicine entitled "Rare Diseases: Hearing and Sight Loss", European Science Foundation, Sant Feliu de Guixols, Spain, 22-27 November, 2009.
- "microRNAs associated with development of the zebrafish inner ear" 7th Molecular Biology of Hearing and Deafness Conference, Boston, MA, 20-23 June, 2009.
- "Development of the Inner Ear" and "Zebrafish Inner Ear Development", Invited speaker and course instructor for the 3rd EuroHear FP6 Project's annual theoretical training, entitled "Development and Genetics of the Inner Ear". Venice, Italy, 23-27 June, 2008.
- "Exploring the function of microRNAs in the specification of sensory organ and hair cell fate" 6th Triennial Molecular Biology of Hearing and Deafness Conference, Hinxton, United Kingdom, July 11-14, 2007.
- "Principles and Issues in Inner Ear Development", Instructor and Invited Symposium Speaker, Woods Hole Summer Course entitled "Biology of the Inner Ear: Experimental and Analytical Approaches", Woods Hole, MA, August 19-26, 2007.
- Battisti A. C., K.N. Fantetti, B.A. Moyers and D.M. Fekete, 2014. A subset of chicken statoacoustic ganglion neurites are repelled by Slit1 and Slit2. Hearing Research 310: 1-12.
- Jiang, H., L. Wang, K. T. Beier, C. L. Cepko, D.M. Fekete and J. V. Brigande. 2013. Lineage analysis of the late otocyst stage mouse inner ear by transuterine microinjection of a retroviral vector encoding alkaline phosphatase and an oligonucleotide library. PLOS ONE 2013 Jul 25;8(7):e69314. doi: 10.1371/journal.pone.0069314.
- Stoller, M.L., H. C. Chang and D. M. Fekete. 2013. Bicistronic gene transfeer tools for delivery of miRNAs and protein coding sequences. International Journal of Molecular Science, 14(9):18239-55. doi: 10.3390/ijms140918239.
- Groves, A.K., K.D. Zhang and D.M. Fekete, 2013. The genetics of hair cell development and regeneration. Annual Reviews of Neuroscience, 36: 361-381.
- Munnamalai, V. and D.M. Fekete, 2013. Wnt signaling during cochlear development. Seminars in Cell and Developmental Biology. 14: 480-489.
- Groves, A.K. and D.M. Fekete. 2012. Shaping sound in space: the regulation of inner ear patterning. Development, Development 139: 245-257.
- Fantetti, K.N. and D.M. Fekete. 2011. Members of the BMP, Shh and FGF morphogen families promote statoacoustic ganglion neurite outgrowth and neuron survival in vitro. Developmental Neurobiology, 72: 1213-1228.
- Fantetti, K.N. and D.M. Fekete. 2011. Dissection and culture of chick statoacoustic ganglion and spinal cord explants in collagen gels for neurite outgrowth assays. JoVE (Journal of Visualized Experiments), (58), e3600, DOI: 10.3791/3600 (2011). .
- Fantetti, K.N, Y. Zou and D.M. Fekete. 2011. Wnts and Wnt inhbitors do not influence axon outgrowth from chicken statoacoustic ganglion neurons. Hearing Research, 278: 86-95.
- Sienknecht, U.J., B.K. Anderson, R.M. Parodi, K.N. Fantetti and D.M. Fekete. 2011. Non-cell-autonomous planar cell polarity propagation in the auditory sensory epithelium of vertebrates. Developmental Biology, 352:27-39.
- Liang, H., D. M. Fekete and O. Andrisani. 2011. CtBP2 down-regulation during neural crest specification induces expression of Mitf and REST, resulting in melanocyte differentiation and sympathoadrenal lineage suppression. Molecular and Cellular Biology, 31:955-970.
- Kilpatrick, L.A., Q. Li, J. Yang, J. C. Goddard, D. M. Fekete, H. Lang. 2011. Adeno-associated virus-mediated gene delivery into the scala media of the normal and deafened adult mouse ear, Gene Therapy. advance online publication 6 January 2011; doi: 10.1038/gt.2010.175
- Li, H., W. Kloosterman and D.M. Fekete. 2010. MicroRNA-183 family members regulate sensorineural fates in the inner ear. Journal of Neuroscience. 30: 3254-3263.
- Abraira, V.E., T. Satoh, D.M. Fekete and L. V. Goodrich. 2010. Vertebrate Lrig3-ErbB interactions occur in vitro but are unlikely to play a role in Lrig3-dependent inner ear morphogenesis. PLoS ONE, 01 Feb 2010 | 10.1371/journal.pone.0008981.
- Li, H. and D.M.Fekete. 2010. MicroRNAs in hair cell development and deafness. Current Opinion in Otolaryngology and Head and Neck Surgery. 18:459-465.
- Friedman, L.M., A.A. Dror, E. Mor, T. Tenne, G. Toren, T. Satoh, D.J. Biesemeier, N. Shomron, D.M. Fekete, E. Hornstein and K.B. Avraham. 2009. MicroRNAs are essential for development and function of inner ear hair cells in vertebrates. PNAS, 106:7915-7920.
- Sienknecht, U.J. and D.M. Fekete. 2009. Mapping of Wnt, Frizzled and Wnt inhibitor gene expression domains in the avian otic primordium. Journal of Comparative Neurology, 517: 751-764.
- Satoh, T. and D. M. Fekete 2008. Lineage analysis of inner ear cells using genomic tags for clonal identification. In: Auditory and Vestibular Research: Methods and Protocols (B. Sokalowski, ed.). Methods in Molecular Biology, 493: 47-63.
- Fekete, D.M. Development of the ear. 2008. In: Inborn Errors of Development, (C.J. Epstein, R.P. Erickson and W. Wynshaw-Boris, eds.) Oxford University Press, Second Edition.
- Fekete, D.M. and U.J. Sienknecht. 2007. Inner ear. In: Sally A Moody (ed.), Principles of Developmental Genetics, Elsevier Press, pp. 631-655.
Professional Faculty Research
(Neuroscience and Developmental Biology) Development of the inner ear