Bernd Fritzsch

A. Personal Statement

I have been a leader in the field of inner ear neuroembryology and evolution for almost 40 years, have organized multiple conferences, books and special journal editions, published over 300 PubMed indexed papers and have received over 24,000 citations for my work. My contributions to the field are both conceptual, development and of novel testable hypothesis, and provides novel techniques and their combination with other methods. The goal of my research is to understand basic aspects of specification, development and maintenance of aging of the neurosensory system of the ear and its connection to the brain using genetically engineered mice to achieve conditional or global deletion of genes or their targeted overexpression (GoF and LoF approach). The specific genes I am focusing on are those relevant to specify the prosensory domains, initiate differentiation of sensory neurons, hair cells and cochlear nucleus neurons.

From 2008 -2016 I was the DEO (Chair) of the Department of Biology at the University of Iowa. More recently I developed a viable conditional deletion mouse model that allows to expand earlier embryonic work on neurotrophin function for the inner ear on neuron viability into the postnatal phase. While I continue my work on the molecular basis of neurosensory development and maintenance to help others by fine tuning their approach toward restauration of lost hair cells and neurons, my additional work as the Director of the University of Iowa Aging Mind and Brain Initiative as well as the Center on Aging, confronted me with the reality of the baby boomer generation that will face in the next 25-35 years: loss of hearing followed by balance impairment. I therefore redirected my efforts to embark on a new line of research that could provide a better molecular understanding of the underlying aging brain molecular changes, expanding on our own and others work on BDNF function in brain plasticity. My recently applied PPG will allow us to use fluorescent genes to study age dependent mice defects in the vestibular connection and function.

While the involvement of neurotrophins in early ear innervation development has been clarified with appropriate techniques by us and others, neither the possible changes in the BDNF signaling system in the vestibular system with age nor the effect of targeted deletions of BDNF with delay or in one or more central nuclei has been studied in detail. In part, this relates to the simple fact that techniques allowing such an investigation at the nuclear and cellular level are only now possible. It also relates to the fact that various cre lines that allow targeted temporal or topographically restricted lesions were not possible just a few years ago. We have been establishing such novel techniques to quantify at a cellular level the expression using RNAscope in conjunction with qPCR and specific immunocytochemistry to allow nuclear and cellular specific quantification, including all relevant components of the BDNF signaling complex to fully understand how BDNF signaling can enable or disable plasticity, dendritic growth and cell survival. We combine these approaches with novel imaging techniques for neurotrophin receptor expression to full quantify both receptor and ligand expression.

1. Fritzsch B, Straka H (2014) Evolution of vertebrate mechanosensory hair cells and inner ears: toward identifying stimuli that select mutation driven altered morphologies. J Comp Physiol A Neuroethol Sens Neural Behav Physiol 200: 5-18.
2. Elliott KL, Pavlínková G, Chizhikov VV, Yamoah EN, Fritzsch B (2021) Development in the Mammalian Auditory System Depends on Transcription Factors. International Journal of Molecular Sciences 22 (8), 4189
3. Rubel EW, Fritzsch B (2002) Auditory system development: primary auditory neurons and their targets. Annu Rev Neurosci 25: 51-101.
4. Fritzsch B, Tessarollo L, Coppola E, Reichardt LF (2004) Neurotrophins in the ear: their roles in sensory neuron survival and fiber guidance. Prog Brain Res 146: 265-278.