Faculty Member Information
Bernd FritzschBernd Fritzsch
Professor & Chair
PhD Technical University of Darmstadt 1978
143 BB
(319) 353-2969
bernd-fritzsch@uiowa.edu
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Ear and hair cell development, regeneration, and evolution

Ongoing research in the Fritzsch laboratory focuses on four main themes:

- Molecular basis of ear development (currently funded by NIH/NIDCD R01)
- Molecular basis of inner ear efferent and brainstem motoneuron formation (currently funded as a subcontract of an NIH R01 with Children's Hospital, Boston)
- Molecular basis of hair cell proliferation, maintenance and regeneration
- Improving multicolor dye tracing techniques (currently funded by NIH/NIMH SBIR II)

Molecular Basis of Ear Development
Research on the molecular basis of ear development analysis, various mutations (knockouts, knockins, transgenic misexpression) of transcription factors (bHLH, Lim homeodomain, GATA, Pax, Eya), or diffusible factors (Fgfs, Wnts, Erbs). This mutational analyses provides in vivo data that help resolve, in collaboration with other laboratories nationally and internationally, the molecular interactions of normal ear development as well as aberrant development underlying congenital ear defects. Superimposed on this proximate analysis is the ultimate question: resolving evolution of the mammalian ear as a transformation of embryonic developmental programs to generate an improved system for sound perception.

Current analysis focuses on:
The role of miRNA on ear and hair cell development (collaboration with Dr. G. Soukup, Creighton University)
The role of Lim domain factors (Isl1, Lmx1a) in ear and hair cell development (collaboration with Drs. D. Nichols and K. Beisel, Creighton University; Dr. K. Millen, University of Chicago; Dr. L. Gan, University of Rochester).
The role of Fgfs, Gata3, Pax2/8, Sox2, Eya 1 and Neurog1 in cochlea neurosensory development (collaborations with Dr. K. Chea, Hong Kong; Dr. P. Xu, Einstein University; Dr. S. Mansour, Salt Lake City; Drs. M. Bouchard and M. Busslinger, Vienna and Montreal).
The role of neurotrophins in neurosensory support (collaborations with Drs. L. Tessarollo, NCI; L. Minichiello, EMBL; S. Green, U Iowa; K. Beisel, Creighton University; H. Staeker, University of Kansas City)

Molecular Basis of Inner Ear Efferent and Brainstem Motoneuron Formation
The research on brainstem motoneurons is aimed to understand the evolution of novel motor outputs of the brainstem such as the evolution and development of eye muscles and their innervation and the evolution and development of the inner ear efferent system that modifies neurosensory information acquisition in the ear. These novelties are embedded in a fairly rigid framework of rhombomeric hindbrain development governed by the highly conserved homeobox genes as well as other transcription factors.

Current analysis centers around two main themes:
The molecular basis of ocular muscle formation and connection development in mice (collaboration with Dr. E. Engle, Children Hospital, Boston)
Molecular basis of inner ear efferent development using conditional mutations of Gata3 or homeobox gene knockout or knockins (collaboration with Drs. G. Gaufo, University of Texas at San Antonio; F. Rijili, Basel; E. Wong, Hong Kong).
Molecular basis of cochlear nucleus and cerebellar development using conditional mutations for Atoh1 and Neurod1 (collaboration with Drs. S. Maricich and H. Zoghbi, Baylor College of Medicine; Dr. J. Lee and I. Jahan, Boulder and U Iowa)

Molecular Basis of Hair Cell Proliferation, Maintenance, and Regeneration
Research on hair cell development and regeneration can be formally divided into two aspects: molecular basis of proliferation regulation and molecular basis of maintenance and differentiation of hair cells.
Proliferation regulation is pursued through mutational dissection of CDK interactions and retinoblastoma/E2F interactions (collaborations with Drs. M. Barbacid, Madrid; Drs. K. Beisel, D. He and S. Rocha-Sanchez, Creighton University)
Maintenance and differentiation of hair cells is investigated in conditional mutants of Atoh1 and mutants of Pou4f3 (collaboration with Drs. H. Zoghbi, Baylor College; K. Beisel, G. Soukup, D. He and L. Hansen, Creighton University).

Improving Multicolor Dye Tracing Techniques
Research on improvement of lipophilic dyes as well as other tracing techniques is focusing on multicolor labeling techniques in combination with in situ and immunocytochemical analyses to maximize data collection from single mutations for optimized high-throughput phenotypic characterization of mutants. Current work focuses on the various aspects of carbocyanine dyes with the ultimate goal in mind to generate multiple (up to eight) dyes that allow independent labeling of various neuronal populations to investigate simultaneously the interactions of multiple neuronal processes to develop synaptic connections (in collaboration with D. M. Nichols, Creighton University and B. Gray, MITT).

Current funding support
2006-2011, RO1, PI, NIDCD “Cellular interactions during ear development”; $ 1,900,000.
2006-2009 NIH SBIR Phase II; Optimizing tracers for multicolor neuronal profiling (Gray, PI; Fritzsch, Co-PI) $515,535 (total for CU).
2007-2012 NIH RO1. Genetic and Anatomic Basis for the Fibrosis Syndrome (Engele, Harvard, PI; Fritzsch, Co-I) $138,098 (total for subcontract).


Selected Publications
Glover J and Fritzsch B. (2008) Brains of Primitive Vertebrates. The New Encyclopedia of Neuroscience. In press.
Fritzsch, B. (2008) Evolution of oculomotor system. Windhorst U, et al., eds. The Encyclopedia of Neuroscience. Springer Verlag, Heidelberg, in press.
Fritzsch B, Nichols D, Gaufo GO. (2008) Evolution of the Hindbrain. Windhorst U, et al., eds. The Encyclopedia of Neuroscience. Springer Verlag, Heidelberg, in press.
Feng F, Maklad A, Fritzsch B. (2008) Vestibular primary afferent pathways. Windhorst U, et al., eds. The Encyclopedia of Neuroscience. Springer Verlag, Heidelberg, in press.
Zou D, Erickson C, Kim E-H, Fritzsch B, Huang L, Xu P-X. (2008) Eya1 acts as a dosage-sensitive regulator for sensory organ development in the mammalian inner ear. Human Mol Genet. [Epub ahead of print] http://www.ncbi.nlm.nih.gov/sites/entrez
Beisel K, Hansen L, Soukup G, Fritzsch B. (2008) Regenerating cochlear hair cells: quo vadis stem cell. Cell & Tissue Res. [Epub ahead of print] http://www.ncbi.nlm.nih.gov/sites/entrez
Cunningham D D, Meng Z, Fritzsch B, Casey ES. (2008) Cloning and developmental expression of the soxB2 genes, sox14 and sox21, during Xenopus laevis embryogenesis. Int J Dev Biol. In press.
Pauley S, Kopecky B, Beisel K, Soukup G, Fritzsch B. (2008) Stem cells and molecular strategies to restore hearing. Panminerva Medica. 50:41-53. http://www.ncbi.nlm.nih.gov/sites/entrez
Okoruwa RE, Weston MD, Sanjeevi DC, Millemon AR, Fritzsch B, Hallworth R, Beisel KW. (2008) Evolutionary insights into the unique electromotility motor of mammalian outer hair cells. Evol Dev. 10: 300-315. http://www.ncbi.nlm.nih.gov/sites/entrez
Ronca AE, Fritzsch B, Bruce LL, Alberts JR. (2008) Orbital spaceflight during pregnancy shapes the function of of the mammalian vestibular system. Behav Neurosci. 122(1):224-32. http://www.ncbi.nlm.nih.gov/sites/entrez
Pierce, M, Weston, M, Fritzsch B, Gabel, H, Ruvkun, G, Soukup, G. (2008) MicroRNA 183 shows conserved expression in sensory neurons across phyla. Evol Dev. 10:106-113. http://www.ncbi.nlm.nih.gov/sites/entrez
Jensen-Smith H, Gray B, Muirhead K, Ohlsson-Wilhelm B, Fritzsch B. (2007) Long-distance three-color neuronal tracing in fixed tissue using NeuroVue dyes. Immunol Invest. 36:763-789. http://www.ncbi.nlm.nih.gov/sites/entrez
Giraldez F, Fritzsch B. (2007) In pursuit of communication: an interview with Bob Ruben. Int. J Dev Biol. 51: 427.
Giraldez F, Fritzsch B. (2007) The molecular biology of ear development - "Twenty years are nothing." Int J Dev Biol. 51: 429-38. http://www.ncbi.nlm.nih.gov/sites/entrez
Fritzsch B, Beisel KW, Pauley S, Soukup G. (2007) Molecular evolution of the vertebrate mechanosensory cell and ear. Int J Dev Biol. 51: 663-678. http://www.ncbi.nlm.nih.gov/sites/entrez
Longo-Guess CM, Gagnon LH, Fritzsch B, Johnson KR. (2007) Targeted knockout and lacZ reporter expression of the mouse Tmhs deafness gene and characterization of the hscy-2J mutation. Mamm Genome. 18:646-656. http://www.ncbi.nlm.nih.gov/sites/entrez
Puligilla C, Feng F, Ishikawa K, Bertuzzi S, Dabdoub A, Griffith AJ, Fritzsch B, Kelley MW. (2007) Disruption of fibroblast growth factor receptor 3 signaling results in defects in cellular differentiation, neuronal patterning, and hearing impairment. Dev Dyn. 236:1905-1917. http://www.ncbi.nlm.nih.gov/sites/entrez
Beisel KW, He D, Hallworth R, and Fritzsch B. (2007) Genetics of Mechanoreceptor Evolution and Development. In: Audition, Vol. 1. (R. Hoy, P. Dallos, eds.). Elsevier, NY, Vol 3, 75-105.
Rocha-Sanchez SM, Morris KA, Kachar B, Nichols D, Fritzsch B, Beisel, KW. (2007) Developmental expression of Kcnq4 in vestibular neurons and neurosensory epithelia. Brain Res. 1139:117-125. http://www.ncbi.nlm.nih.gov/sites/entrez