Bernd Fritzsch

Bernd Fritzsch
University of Iowa | UI · Department of Biology

Ph.D., TU Darmstadt, 1978

About

507
Publications
57,600
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19,234
Citations
Introduction
My work concentrates on the molecular development and evolution of neurosensory cells of the ear. Ultimately, the understanding of the molecular interactions should help us provide a rational basis to intervene hair cell loss and ultimately initial regeneration.
Additional affiliations
December 2019 - January 2020
University of Iowa
Position
  • Retired
June 2014 - July 2018
University of Iowa
Position
  • Managing Director
March 2014 - June 2019
University of Iowa
Position
  • Managing Director

Publications

Publications (507)
Article
Full-text available
Early in vertebrate evolution, a single homeobox (Hox) cluster in basal chordates was quadrupled to generate the Hox gene clusters present in extant vertebrates. Here we ask how this expanded gene pool may have influenced the evolution of the visual system. We suggest that a single neurosensory cell type split into ciliated sensory cells (photorece...
Book
This book is an overview of primary sensory maps of vertebrates, characterized by continuous and discrete properties. The eight primary sensory maps of vertebrates have unique features and use distinct molecular cues, cell cycle exit, and activity combinations during development, regeneration, and plasticity. As an introduction and overview, the bo...
Preprint
A conserved line of polarity reversal (LPR) demarcates hair cells into two regions of opposite orientation in the otolith organs of the inner ear. The functional significance of this arrangement is not known. Using gene knockout and conditional knockouts (cKO) mice, we show that the Emx2 encoded transcription factor establishes the LPR and bidirect...
Article
Full-text available
Neuronal development in the inner ear is initiated by expression of the proneural basic Helix-Loop-Helix (bHLH) transcription factor Neurogenin1 that specifies neuronal precursors in the otocyst. The initial specification of the neuroblasts within the otic epithelium is followed by the expression of an additional bHLH factor, Neurod1. Although NEUR...
Article
Full-text available
Age-related hearing loss (ARHL) is a common, increasing problem for older adults, affecting about 1 billion people by 2050. We aim to correlate the different reductions of hearing from cochlear hair cells (HCs), spiral ganglion neurons (SGNs), cochlear nuclei (CN), and superior olivary complex (SOC) with the analysis of various reasons for each one...
Article
Diverse neurons in the parabrachial nucleus (PB) communicate with widespread brain regions. Despite evidence linking them to a variety of homeostatic functions, it remains difficult to determine which PB neurons influence which functions because their subpopulations intermingle extensively. An improved framework for identifying these intermingled s...
Article
Full-text available
The vestibular system is vital for proper balance perception, and its dysfunction contributes significantly to fall-related injuries, especially in the elderly. Vestibular ganglion neurons innervate vestibular hair cells at the periphery and vestibular nuclei and the uvula and nodule of the cerebellum centrally. During aging, these vestibular gangl...
Preprint
A cardinal feature of the auditory pathway is frequency selectivity, represented in the form of a tonotopic map from the cochlea to the cortex. The molecular determinants of the auditory frequency map are unknown. Here, we discovered that the transcription factor ISL1 regulates molecular and cellular features of auditory neurons, including the form...
Article
Full-text available
Four sensory systems (vestibular, lateral line, electroreception, auditory) are unique and project exclusively to the brainstem of vertebrates. All sensory neurons depend on a common set of genes (Eya1, Sox2, Neurog1, Neurod1) that project to a dorsal nucleus and an intermediate nucleus, which differentiate into the vestibular ear, lateral line and...
Article
Full-text available
The two types of spiral ganglion neurons (SGNs), types I and II, innervate inner hair cells and outer hair cells, respectively, within the mammalian cochlea and send another process back to cochlear nuclei in the hindbrain. Studying these two neuronal types has been made easier with the identification of unique molecular markers. One of these marke...
Article
Full-text available
We review the molecular basis of three related basic helix–loop–helix (bHLH) genes (Neurog1, Neurod1, and Atoh1) and upstream regulators Eya1/Six1, Sox2, Pax2, Gata3, Fgfr2b, Foxg1, and Lmx1a/b during the development of spiral ganglia, cochlear nuclei, and cochlear hair cells. Neuronal development requires early expression of Neurog1, followed by i...
Article
Full-text available
We review the molecular basis of several transcription factors (Eya1, Sox2), including the three related genes coding basic helix–loop–helix (bHLH; see abbreviations) proteins (Neurog1, Neurod1, Atoh1) during the development of spiral ganglia, cochlear nuclei, and cochlear hair cells. Neuronal development requires Neurog1, followed by its downstrea...
Article
Full-text available
The trochlear projection is unique among the cranial nerves in that it exits the midbrain dorsally to innervate the contralateral superior oblique muscle in all vertebrates. Trochlear as well as oculomotor motoneurons uniquely depend upon Phox2a and Wnt1, both of which are downstream of Lmx1b, though why trochlear motoneurons display such unusual p...
Article
Full-text available
Specification of Sox2 ⁺ proneurosensory progenitors within otic ectoderm is a prerequisite for the production of sensory cells and neurons for hearing. However, the underlying molecular mechanisms driving this lineage specification remain unknown. Here, we show that the Brg1-based SWI/SNF chromatin-remodeling complex interacts with the neurosensory...
Article
Full-text available
The sense of hearing depends on a specialized sensory organ in the inner ear, called the cochlea, which contains the auditory hair cells (HCs). Noise trauma, infections, genetic factors, side effects of ototoxic drugs (ie, some antibiotics and chemotherapeutics), or simply aging lead to the loss of HCs and their associated primary neurons. This res...
Book
The seven volumes of the second edition of The Senses: A Comprehensive Reference follow the principle of the first edition but are expanded to provide a novel second edition. Major restructuring will be presented by “Vision” (Vol 1; Paul Martin), “Auditory” (Vol 2; Benedikt Grothe), “Olfaction and Taste” (Vol 3; Wolfgang Meyerhof), “Somatosensation...
Article
The inner ear, projections, and brainstem nuclei are essential components of the auditory and vestibular systems. It is believed that the evolution of complex systems depends on duplicated sets of genes. The contribution of duplicated genes to auditory or vestibular system development, however, is poorly understood. We describe that Lmx1a and Lmx1b...
Article
Full-text available
Ear development requires the transcription factors ATOH1 for hair cell differentiation and NEUROD1 for sensory neuron development. In addition, NEUROD1 negatively regulates Atoh1 gene expression. As we previously showed that deletion of the Neurod1 gene in the cochlea results in axon guidance defects and excessive peripheral innervation of the sens...
Article
Full-text available
In mechanosensory hair cells (HCs) of the ear, the transcriptional repressor REST is continuously inactivated by alternative splicing of its pre-mRNA. This mechanism of REST inactivation is crucial for hearing in humans and mice. Rest is one of many pre-mRNAs whose alternative splicing is regulated by the splicing factor SRRM4; Srrm4 loss-of-functi...
Article
Full-text available
The LIM homeodomain transcription factor Lmx1a shows a dynamic expression in the developing mouse ear that stabilizes in the non-sensory epithelium. Previous work showed that Lmx1a functional null mutants have an additional sensory hair cell patch in the posterior wall of a cochlear duct and have a mix of vestibular and cochlear hair cells in the b...
Article
Objectives The objective was to explore the effect of the proneuronal transcription factor neurogenic differentiation 1 (Neurod1, ND1) on Schwann cells (SC) and schwannoma cell proliferation. Methods Using a variety of transgenic mouse lines, we investigated how expression of Neurod1 effects medulloblastoma (MB) growth, schwannoma tumor progressio...
Article
Age-related hearing loss (ARHL) is the most prevalent age-related sensory deficit. ARHL reduces the quality of life of the growing aging population, setting seniors up for the enhanced mental decline. The size of the needy population, the structural deficit, and a likely research strategy for effective treatment of chronic neurosensory hearing in t...
Article
Full-text available
The non-conventional neurotrophic factor mesencephalic astrocyte-derived neurotrophic factor (MANF) is an endoplasmic reticulum (ER)-resident protein that promotes ER homeostasis. MANF has a cytoprotective function, shown in the central nervous system neurons and pancreatic beta cells. Here, we report that MANF is expressed in the hair cells and ne...
Article
Full-text available
The transcription factor Six1 is essential for induction of sensory cell fate and formation of auditory sensory epithelium, but how it activates gene expression programs to generate distinct cell-types remains unknown. Here, we perform genome-wide characterization of Six1 binding at different stages of auditory sensory epithelium development and fi...
Chapter
Full-text available
Synopsis Mechanosensation at its core requires opening transmembrane proteins through mechanical forces. Such forces can act within the lipid bilayer (force-by-lipid) or though intracellular and/or extracellular connections (force-by-tether). Building on the assumption that specialized, tethered mechanotransduction channels evolved from lipid embed...
Chapter
Synopsis We review the lateral line and electroreceptor systems among craniates and highlight unique gains and losses. Distinctive features permit grouping of derived animals with respect to similarities (stereocilia and kinocilia length) and share with a single afferent versus two afferents among electroreceptors and lateral line, respectively. Tr...
Article
Full-text available
The evolutionary diversification of animals is one of Earth's greatest marvels, yet its earliest steps are shrouded in mystery. Animals, the monophyletic clade known as Metazoa, evolved wildly divergent multicellular life strategies featuring ciliated sensory epithelia. In many lineages epithelial sensoria became coupled to increasingly complex ner...
Article
Full-text available
Transcription factor Neurod1 is required for enteroendocrine progenitor differentiation and maturation. Several earlier studies indicated that ectopic expression of Neurod1 converted non- neuronal cells into neurons. However, the functional consequence of ectopic Neurod1 expression has not been examined in the GI tract, and it is not known whether...
Article
Full-text available
Npr2 (natriuretic peptide receptor 2) affects bifurcation of neural crest or placode-derived afferents upon entering the brain stem/spinal cord, leading to a lack of either rostral or caudal branches. Previous work has shown that early embryonic growth of cochlear and vestibular afferents is equally affected in this mutant but later work on postnat...
Article
SOX2 is essential for maintaining neurosensory stem cell properties, although its involvement in the early neurosensory development of cranial placodes remains unclear. To address this, we used Foxg1-Cre to conditionally delete Sox2 during eye, ear, and olfactory placode development. Foxg1-Cre mediated early deletion of Sox2 eradicates all olfactor...
Preprint
Full-text available
The evolutionary diversification of animals is one of nature's greatest mysteries. In addition, animals evolved wildly divergent multicellular life strategies featuring ciliated sensory epithelia. In many lineages epithelial sensoria became coupled to increasingly complex nervous systems. Currently, different phylogenetic analyses of single-copy ge...
Article
Full-text available
Inner ear sensory afferent connections establish sensory maps between the inner ear hair cells and the vestibular and auditory nuclei to allow vestibular and sound information processing. While molecular guidance of sensory afferents to the periphery has been well studied, molecular guidance of central projections from the ear is only beginning to...
Article
Full-text available
Central nervous system neurons become postmitotic when radial glia cells divide to form neuroblasts. Neuroblasts may migrate away from the ventricle radially along glia fibers, in various directions or even across the midline. We present four cases of unusual migration that are variably connected to either pathology or formation of new populations...
Article
Full-text available
Interaction with the world around us requires extracting meaningful signals to guide behavior. Each of the six mammalian senses (olfaction, vision, somatosensation, hearing, balance, and taste) has a unique primary map that extracts sense-specific information. Sensory systems in the periphery and their target neurons in the central nervous system d...
Cover Page
Full-text available
This cover of Journal of Neuroscience of February 6th issue shows the effect of conditional deletion of Neurod1 using Isli1-cre on spiral ganglion neurons (red) and olivocochler efferents (green) innervation of the organ of Corti, the mammalian hearing organ. The cover was chosen by the Journal of Neuroscience staff form images presented in the art...
Article
Full-text available
Primary sensory afferents project to the CNS in an organized fashion, creating sensory maps in target areas. In the auditory system, spiral ganglion neurons in-nervate different portions of the organ of Corti from base to apex, and their central projections maintain this order as they in-nervate cochlear nuclei, where they create a cochleotopic-and...
Article
Full-text available
Hearing depends on extracting frequency, intensity, and temporal properties from sound to generate an auditory map for acoustical signal processing. How physiology intersects with molecular specification to fine tune the developing properties of the auditory system that enable these aspects remains unclear. We made a novel conditional deletion mode...
Article
Full-text available
RNAscope® technology provided by Advanced Cell Diagnostics (ACD) allows the detection and evaluation of coinciding mRNA expression profiles in the same or adjacent cells in unprecedented quantitative detail using multicolor fluorescent in situ hybridization (FISH). While already extensively used in thinly sectioned material of various pathological...
Article
Full-text available
The cover image is based on the Original Article Transplantation of Ears Provides Insights into Inner Ear Afferent Pathfinding Properties by Clayton Gordy et al., DOI: 10.1002/dneu.22629. Please see Figure 6 for detailed description.
Article
Full-text available
The inner ear and its two subsystems, the vestibular and the auditory system, exemplify how the identification of distinct cellular or anatomical elements ahead of elucidating their function, leads to a medley of anatomically defined and recognition oriented names that confused generations of students. Past attempts to clarify this unyielding nomen...
Preprint
Full-text available
Otic ectoderm gives rise to almost all cell types of the inner ear; however, the mechanisms that link transcription factors, chromatin, lineage commitment and differentiation capacity are largely unknown. Here we show that Brg1 chromatin-remodeling factor is required for specifying neurosensory lineage in the otocyst and for inducing hair and suppo...
Article
Full-text available
Vertebrate inner ear neurons project into the correct brainstem nuclei region before target neurons become postmitotic, or even in their absence. Moreover, afferents from transplanted ears in frogs have been shown to navigate to vestibular nuclei, suggesting that ear afferents use molecular cues to find their target. We performed heterochronic, xen...
Article
Full-text available
We review the evolution and development of organ of Corti hair cells with a focus on their molecular differences from vestibular hair cells. Such information is needed to therapeutically guide organ of Corti hair cell development in flat epithelia and generate the correct arrangement of different hair cell types, orientation of stereocilia, and the...
Article
Numerous tissue transplantations have demonstrated that otocysts can develop into normal ears in any location in all vertebrates tested thus far, though the pattern of innervation of these transplanted ears has largely been understudied. Here, expanding on previous findings that transplanted ears demonstrate capability of local brainstem innervatio...
Article
Full-text available
The mammalian hearing organ is a regular array of two types of hair cells (HCs) surrounded by six types of supporting cells. Along the tonotopic axis, this conserved radial array of cell types shows longitudinal variations to enhance the tuning properties of basilar membrane. We present the current evidence supporting the hypothesis that quantitati...
Book
A thought-provoking treatise on understanding and treating the aging mind and brain This handbook recognizes the critical issues surrounding mind and brain health by tackling overarching and pragmatic needs so as to better understand these multifaceted issues. This includes summarizing and synthesizing critical evidence, approaches, and strategies...
Article
Full-text available
The mammalian hearing organ is a stereotyped cellular assembly with orderly innervation: two types of spiral ganglion neurons (SGNs) innervate two types of differentially distributed hair cells (HCs). HCs and SGNs evolved from single neurosensory cells through gene multiplication and diversification. Independent regulation of HCs and neuronal diffe...
Article
Full-text available
Purpose/aim To summarize and discuss how geriatric dentistry has been addressed in dental schools of different countries regarding to (1) teaching students at the predoctoral level; (2) advanced training, and (3) research. Method and materials A convenience sample of faculty members from a selection of high, upper‐middle and lower‐middle income co...
Article
Wilhelm His (1831-1904) provided lasting insights into the development of the central and peripheral nervous system using innovative technologies such as the microtome, which he invented. 150 years after his resurrection of the classical germ layer theory of Wolff, von Baer and Remak, his description of the developmental origin of cranial and spina...
Article
Full-text available
To determine whether responses during infrared neural stimulation (INS) result from the direct interaction with spiral ganglion neurons (SGNs), we tested three genetically modified deaf mouse models: Atoh1-cre; Atoh1 f/f (Atoh1 conditional knockout, CKO), Atoh1-cre; Atoh1 f/kiNeurog1 (Neurog1 knockin, KI), and the Vglut3 knockout (Vglut3 -/-) mice....
Article
Cover: The cover, by Sanam Zarei et al., is based on the Research Article Sonic hedgehog antagonists reduce size and alter patterning of the frog inner ear, DOI: 10.1002/dneu.22544.
Article
Full-text available
Several concepts developed in the nineteenth century have formed the basis of much of our neuroanatomical teaching today. Not all of these were based on solid evidence nor have withstood the test of time. Recent evidence on the evolution and development of the autonomic nervous system, combined with molecular insights into the development and diver...
Article
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Sonic Hedgehog (Shh) signaling plays a major role in vertebrate development, from regulation of proliferation to the patterning of various organs. In amniotes, Shh affects dorsoventral patterning in the inner ear but affects anteroposterior patterning in teleosts. Currently, it remains unknown the function of Shh in inner ear development in terms o...
Data
Table S6. Gene Ontology Analysis of Genes with Bivalently Marked Promoters, Related to Figure 2
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Document S1. Supplemental Experimental Procedures, Figures S1–S4, and Tables S1–S4
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Table S7. Gene Name and Accession Number of Candidate Genes Involved in Mitotic Cell Cycle and Regulation of Neuron Differentiation, Related to Figure 2
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Table S8. Identified E-BOXES 1 kb Upstream of TSS in Mitotic Cell-Cycle Genes, Related to Figure 2
Data
Table S9. Identified E-Boxes 1 kb Upstream of TSS in Regulation of Neuron Differentiation Genes, Related to Figure 2