The University of Iowa
College of Liberal Arts and Sciences
The Department of Biology

Faculty Information

Bernd Fritzsch

Bernd Fritzsch

Professor & Chair
PhD, Technical University of Darmstadt 1978
143 BB
(319) 353-2969
bernd-fritzsch@uiowa.edu

https://www.biology.uiowa.edu/labs/fritzsch/
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Ear and hair cell development, regeneration, and evolution

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

  1. Molecular basis of ear development (currently funded by NIH/NIDCD R01)
  2. Molecular basis of inner ear efferent and brainstem motoneuron formation (currently funded as a subcontract of an NIH R01 with Children's Hospital, Boston)
  3. Molecular basis of hair cell proliferation, maintenance and regeneration
  4. 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:

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:

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).

Professor Fritzch is Associate Director of the Aging Mind and Brain Initiative.

 

Current funding support

2009-2014 NIH/NIDCD R01. Role of MicroRNAs in Mammalian Ear Development and Neurosensory Specification (Soukup PI, Fritzsch Consultant) $17,500
2007-2012 NIH RO1. Genetic and Anatomic Basis for the Fibrosis Syndrome (Engele, Harvard, PI; Fritzsch, Co-I) $138,098 (total for subcontract)

2010-2015 P30 NIH/NIDCD. Iowa Center for Molecular Auditory Neuroscience (Green PI, Dailey, Eberl, Fritzsch, Hansen, Lee Co-Is) $1,699,460 direct costs



Selected Publications

Yang, T., Jia, Z., Bryant-Pike, W., Chandrasekhar, A., Murray, J.C., Fritzsch, B., Bassuk, A.G. (2014) Analysis of PRICKLE1 in human cleft palate and mouse development demonstrates rare and common variants involved in human malformations. Mol Genet Genomic Med, 17 Dec DOI:10.1002/mgg3.53.

Maklad, A., Reed, C., Johnson, N.S., Fritzsch, B. (2014) Anatomy of the lambrey ear: Morphological evidence for occurrence of horizontal semicircular ducts in the labyrinth of Petromyzon marinus. J Anat, Jan 18 DOI: 10.1111/joa.12159.

Duncan, J.S., Elliot, K.L., Kersigo, J., Gray, B., Fritzsch, B. (2014) Combining whole-mount in situ hybridization with Neuronal tracing and immunohistochemistry. In: (G. Hauptman, Ed.) Neuromethods, in press, New York: Springer.

Straka, H., Glover, J., Fritzsch, B. (2014) Connecting ears to eye muscles: Evolution of a ‘simple’ reflex arc. Brain Behav Evol. In press.

Fritzsch, B., Kopecky, B.J., Duncan, J.S. (2014) Development of the mammalian ‘vestibular’ system: Evo-devo of form development and genes to detect gravity and angular acceleration. In: (R. Romand, I. Varello-Nieto, Eds.) Development of Auditory and Vestibular Systems: Molecular Development of the Inner Ear, in press, Oxford: Elsevier

Sienknecht, U., Fritzsch, B. Köppl, C. (2014) Evolution and development of hair-cell polarity and efferent function in the inner ear. Brain Behav Evol. In press.

Fritzsch, B., Lopez-Schier, H. (2014) Evolution of polarized hair cells in aquatic vertebrates and their connection to directionally sensitive neurons. In: (H. Bleckmann, J. Mogdans, S. Coombs, Eds.) Flow Sensing in Air and Water, pp. 271-294 New York: Springer.

Fritzsch, B., Crapon de Caprona, M.D. (2014) From cells to hearing organs: Altering genes and their expression to evolve novel sensory organs. In (R. Fay and A. Popper, Eds) Springer Handbook of Auditory Research: Development of the Inner Ear Vol 50, in press, New York: Springer.

Zine, A., Löewenheim, H., Fritzsch, B. (2014) Toward translating molecular ear development to generate hair cells from stem cells. In: (K. Turksen, Ed.) Adult Stem Cells DOI: 10.1007/978-1-4614-9569-7_6, New York: Springer.

Chonko, K.T., Jahan, I., Stone, J., Wright, M.C., Fujiyama, T., Hoshino, M. Fritzsch, B., Maricich, S.M. (2013) Atoh1 directs hair cell differentiation and survival in late embryonic mouse inner ear. Dev Biol 1:401-410. PMCID in process

Jahan, I. Pan, N., Kersigo, J. Fritzsch, B. (2013) Beyond generalized hair cells: Molecular cues for hair cell types. Hear Res. 297:30-41. PMCID: PMC3624765

Duncan, J.S., Fritzsch, B. (2013) Continued expression of GATA3 is necessary for cochlear neurosensory development. PLoS One. 8:e62046. PMCID: PMC3628701

Kopecky, B. Jahan I, and Fritzsch, B. (2013). Correct timing of proliferation and differentiation is necessary for normal inner ear development and auditory hair cell viability. Dev Dyn. 242:132-147. PMCID: PMC3553268

Kopecky, B., Fritzsch, B. (2013) Embryology of the Ear. In (H.V. Toriello and S.D. Smith, Eds.), Hereditary Hearing Loss and Its Syndromes (3rd ed., pp. 13-57). New York: Oxford University Press.

Defourny J, Poirrier AL, Lallemend F, Mateo Sánchez S, Neef J, Vanderhaeghen P, Soriano E, Peuckert C, Kullander K, Fritzsch B, Nguyen L, Moonen G, Moser T, Malgrange B. (2013) Ephrin-A5/EphA4 signaling controls specific afferent targeting to cochlear hair cells. Nat Commun. 4:1438.

Fritzsch B, Pan N, Jahan I, Duncan J, Kopecky B, Elliott K, Kersigo J, Yang T. (2013) Evolution and development of the mammalian auditory system: an Organ of Corti-centric inside-out perspective. Evo Dev. 15:63-79.

Pan, N., Jahan, I., Elliott, K., Kersigo, J., Fritzsch, B. (2013) Evolution of the mammalian auditory system: An integrated perspective of the molecular development. In: (D. Frenz, Ed.) Molecular Signaling of Mammalian Inner Ear Development, pp. 1-26, New York: Nova Science Publishers.

Tang, J., Pecka, J.I., Fritzsch, B., Beisel, K.W., He, D.Z.Z. (2013) Lizard and frog prestin: evolutionary insight into functional changes. PLoS One, 8:e54388. PMCID: PMC3546999

Yang, T., Bassuk, A.G., Fritzsch, B. (2013) Prickle1 stunts limb growth through alternation of cell polarity and gene expression. Dev Dyn DOI: 10.1002/dvdy.24025.

Smith JJ, Kuraku S, Holt C, Sauka-Spengler T, Jiang N, Campbell MS, Yandell MD, Manousaki T, Meyer A, Bloom OE, Morgan JR, Buxbaum JD, Sachidanandam R, Sims C, Garruss AS, Cook M, Krumlauf R, Wiedemann LM, Sower SA, Decatur WA, Hall JA, Amemiya CT, Saha NR, Buckley KM, Rast JP, Das S, Hirano M, McCurley N, Guo P, Rohner N, Tabin CJ, Piccinelli P, Elgar G, Ruffier M, Aken BL, Searle SM, Muffato M, Pignatelli M, Herrero J, Jones M, Brown CT, Chung-Davidson YW, Nanlohy KG, Libants SV, Yeh CY, McCauley DW, Langeland JA, Pancer Z, Fritzsch B, de Jong PJ, Zhu B, Fulton LL, Theising B, Flicek P, Bronner ME, Warren WC, Clifton SW, Wilson RK, Li W. (2013) Sequencing of the sea lamprey (Petromyzon marinus) genome provides insights into vertebrate evolution. Nat. Genet. 45:415-421. PMCID in process.

Elliott, K., Houston, D., Fritzsch, B. (2013) Transplantation of Xenopus laevis tissues to determine the ability of motor neurons to acquire a novel target. PLoS One, 8:e55541. PMCID: PMC3562177

O’Neill, P, Mak, S-S, Fritzsch, B., Ladher, R.K., Baker, C.V. (2012) The amniote paratympanic organ develops from a previously undiscovered sensory placode. Nat Commun. 3:1041 PMCID: PMC3518548

Duncan, J.S., Fritzsch, B. (2012) Evolution of sound and balance perception: Innovations that aggregate single hair cells into the ear and transform a gravistatic sensor into the organ of corti. Anat. Rec., 295:1760-1774.

Jahan I, Pan N, Kersigo J, Calisto LE, Morris KA, Kopecky B, Duncan JS, Beisel KW, Fritzsch B. (2012) Expression of Neurog1 instead of Atoh1 can partially rescue organ of Corti cell survival. PLoS One. 7(1):e30853. PubMed PMID: 22292060; PubMed Central PMCID: PMC3265522.

Chen Y, Takano-Maruyama M, Fritzsch B, Gaufo GO. (2012) Hoxb1 controls anteroposterior identity of vestibular projection neurons. PLoS One. 7(4):e34762. PubMed PMID: 22485187; PubMed Central PMCID: PMC3317634.

Fritzsch, B. (2012) Mammalian Genetics (Mouse Genetics). In (S. Maloy and K. Hughes, Eds.), Brenner’s Encyclopedia of Genetics (2nd ed., pp. 300-302). Oxford: Elsevier.

Glasco, D.M., Sittaramane, V., Bryant, W., Fritzsch, B., Sawant, A., Paudyal, A., Stewart, M., Andre, P., Cadete Vilhais-Neto, G., Yang, Y., Song, M.R., Murdoch, J.N., Chandrasekhar, A. (2012). The mouse Wnt/PCP protein Vangl2 is necessary for migration of facial branchiomotor neurons, and functions independently of Dishevelled. Dev Biol. 369:211-22. PMCID: PMC3484895

Nakano Y, Jahan I, Bonde G, Sun X, Hildebrand MS, Engelhardt JF, Smith RJ, Cornell RA, Fritzsch B, Bánfi B. (2012) A mutation in the srrm4 gene causes alternative splicing defects and deafness in the Bronx waltzer mouse , PLoS Genet. 8:e1002966. PMCID: PMC3464207.

Kopecky B, Decook R, Fritzsch B. (2012) Mutational ataxia resulting from abnormal vestibular acquisition and processing is partially compensated for. Behav Neurosci. 126(2):301-13. PubMed PMID: 22309445; PubMed Central PMCID: PMC3314111.

Kopecky, B., DeCook, R. and Fritzsch, B. (2012). N-Myc and L-Myc are essential for hair cell formation but not maintenance. Brain Res. 1484:1-14. PMCID PMC3464207

Fritzsch, B. and Kopecky, B. (2012). Neurosensory Specification and Development. In (S. Maloy and K. Hughes, Eds.), Brenner’s Encyclopedia of Genetics (2nd ed., pp.50-56). Oxford: Elsevier.

Pan N, Jahan I, Kersigo J, Duncan JS, Kopecky B, Fritzsch B. (2012) A novel Atoh1 \"self-terminating\" mouse model reveals the necessity of proper Atoh1 level and duration for hair cell differentiation and viability. PLoS One. 7(1):e30358. PubMed PMID: 22279587; PubMed Central PMCID: PMC3261193.

Kopecky B, Johnson S, Schmitz H, Santi P, Fritzsch B. (2012) Scanning thin-sheet laser imaging microscopy elucidates details on mouse ear development. Dev Dyn. 241(3):465-80. PubMed PMID:
22271591.

Kopecky, B.J., Duncan, J.S., Elliott, K.L., Fritzsch, B. (2012) Three-dimensional reconstructions from optical sections of thick mouse inner ears using confocal microscopy. J. Microsc. 248:292-298. PMCID: PMC3625616

Duncan JS, Fritzsch B. (2012) Transforming the vestibular system one molecule at a time: the molecular and developmental basis of vertebrate auditory evolution. Adv Exp Med Biol. 739:173-86. Review. PubMed PMID: 22399402.