Bernd Fritzsch | The University of Iowa (original) (raw)

Papers by Bernd Fritzsch

F1000 - Post-publication peer review of the biomedical literature, 2015

Cell and Tissue Research, 2015

Brain, Behavior and Evolution, 1988

American Journal of Physiology-Regulatory, Integrative and Comparative Physiology, 2004

CCK type 1 (CCK1) receptor antagonists differing in blood-brain barrier permeability were used to... more CCK type 1 (CCK1) receptor antagonists differing in blood-brain barrier permeability were used to test the hypothesis that satiety is mediated in part by CCK action at CCK1 receptors on vagal sensory nerves innervating the small intestine. Devazepide penetrates the blood-brain barrier; A-70104, the dicyclohexylammonium salt of Nα-3-quinolinoyl-d-Glu- N,N-dipentylamide, does not. At dark onset, non-food-deprived control rats and rats with subdiaphragmatic vagotomies received a bolus injection of devazepide (2.5 μmol/kg iv) or a 3-h infusion of A-70104 (3 μmol·kg−1·h−1 iv) either alone or coadministered with a 2-h intragastric infusion of peptone (0.75 or 1 g/h). Food intake was determined from continuous computer recordings of changes in food bowl weight. In control rats both antagonists stimulated food intake and attenuated the anorexic response to intragastric infusion of peptone. In contrast, only devazepide was effective in stimulating food intake in vagotomized rats. Thus endoge...

Frontiers in Cellular Neuroscience, 2021

The two types of spiral ganglion neurons (SGNs), types I and II, innervate inner hair cells and o... more 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 markers, peripherin, was shown using antibodies to be present in all SGNs initially but becomes specific to type II SGNs during maturation. We used mice with fluorescently labeled peripherin (Prph-eGFP) to examine peripherin expression in SGNs during development and in aged mice. Using these mice, we confirm the initial expression of Prph-eGFP in both types I and II neurons and eventual restriction to only type II perikarya shortly after birth. However, while Prph-eGFP is uniquely expressed within type II cell bodies by P8, both types I and II peripheral and central processes continue to express Prph-eGFP for some time before becoming downregul...

International Journal of Molecular Sciences, Apr 10, 2023

Nature Communications, Sep 4, 2012

Frontiers in Aging Neuroscience, Feb 17, 2022

Scientific Reports, Feb 9, 2015

Brain Sciences

The development of the central auditory system, including the auditory cortex and other areas inv... more The development of the central auditory system, including the auditory cortex and other areas involved in processing sound, is shaped by genetic and environmental factors, enabling infants to learn how to speak. Before explaining hearing in humans, a short overview of auditory dysfunction is provided. Environmental factors such as exposure to sound and language can impact the development and function of the auditory system sound processing, including discerning in speech perception, singing, and language processing. Infants can hear before birth, and sound exposure sculpts their developing auditory system structure and functions. Exposing infants to singing and speaking can support their auditory and language development. In aging humans, the hippocampus and auditory nuclear centers are affected by neurodegenerative diseases such as Alzheimer’s, resulting in memory and auditory processing difficulties. As the disease progresses, overt auditory nuclear center damage occurs, leading t...

Diversity

Four sensory systems (vestibular, lateral line, electroreception, auditory) are unique and projec... more 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 electroreception in vertebrates. In tetrapods, a loss of two sensory systems (lateral line, electroreception) leads to the development of a unique ear and auditory system in amniotes. Lmx1a/b, Gdf7, Wnt1/3a, BMP4/7 and Atoh1 define the lateral line, electroreception and auditory nuclei. In contrast, vestibular nuclei depend on Neurog1/2, Ascl1, Ptf1a and Olig3, among others, to develop an independent origin of the vestibular nuclei. A common origin of hair cells depends on Eya1, Sox2 and Atoh1, which generate the mechanosensory cells. Several proteins define the polarity of hair cells in the ear and lateral line. A unique connection of st...

Frontiers in Aging Neuroscience, 2022

Age-related hearing loss (ARHL) is a common, increasing problem for older adults, affecting about... more 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 on the sensory deficit profiles. Outer HCs show a progressive loss in a basal-to-apical gradient, and inner HCs show a loss in a apex-to-base progression that results in ARHL at high frequencies after 70 years of age. In early neonates, SGNs innervation of cochlear HCs is maintained. Loss of SGNs results in a considerable decrease (~50% or more) of cochlear nuclei in neonates, though the loss is milder in older mice and humans. The dorsal cochlear nuclei (fusiform neurons) project directly to the inferior colliculi while most anterior cochlear nuclei reach the SOC. Reducing the number of neurons in the medial nucleus of the trapezoid body...

Frontiers in Neurology, 2021

The vestibular system is vital for proper balance perception, and its dysfunction contributes sig... more 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 ganglion neurons degenerate, impairing vestibular function. A complete understanding of the molecular mechanisms involved in neurosensory cell survival in the vestibular system is unknown. Brain-derived neurotrophic factor (BDNF) is specifically required for the survival of vestibular ganglion neurons, as its loss leads to early neuronal death. Bdnf null mice die within 3 weeks of birth, preventing the study of the long-term effects on target cells. We use Pax2-cre to conditionally knock out Bdnf, allowing mice survival to approximately 6 months of age. We show that a long-term loss of Bdnf leads to a significant reduction in the number of vest...

Life Science Alliance, 2020

In mechanosensory hair cells (HCs) of the ear, the transcriptional repressor REST is continuously... more 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-function mutation in mice (Srrm4bv/bv) causes deafness, balance defects, and degeneration of all HC types other than the outer HCs (OHCs). The specific splicing alterations that drive HC degeneration in Srrm4bv/bv mice are unknown, and the mechanism underlying SRRM4-independent survival of OHCs is undefined. Here, we show that transgenic expression of a dominant-negative REST fragment in Srrm4bv/bv mice is sufficient for long-term rescue of hearing, balancing, HCs, alternative splicing of Rest, and expression of REST target genes including the Srrm4 paralog Srrm3. We also show that in HCs, SRRM3 regulates many of the same exons as SRRM4; OHCs ar...

Nucleic Acids Research, 2020

The transcription factor Six1 is essential for induction of sensory cell fate and formation of au... more 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 find that Six1-binding to cis-regulatory elements changes dramatically at cell-state transitions. Intriguingly, Six1 pre-occupies enhancers of cell-type-specific regulators and effectors before their expression. We demonstrate in-vivo cell-type-specific activity of Six1-bound novel enhancers of Pbx1, Fgf8, Dusp6, Vangl2, the hair-cell master regulator Atoh1 and a cascade of Atoh1’s downstream factors, including Pou4f3 and Gfi1. A subset of Six1-bound sites carry consensus-sequences for its downstream factors, including Atoh1, Gfi1, Pou4f3, Gata3 and Pbx1, all of which physically interact with Six1. Motif analysis identifies RFX/X-box as one ...

Otic ectoderm gives rise to almost all cell types of the inner ear; however, the mechanisms that ... more 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 supporting cell fates in the cochlear sensory epithelium. Brg1 interacts with the critical neurosensory-specific transcription factors Eya1/Six1, both of which simultaneously interact with BAF60a or BAF60c. Chromatin immunoprecipitation-sequencing (ChIP-seq) and ChIP assays demonstrate Brg1 association with discrete regulatory elements at theEya1andSix1loci.Brg1-deficiency leads to markedly decreased Brg1 binding at these elements and loss ofEya1andSix1expression. Furthermore, ChIP-seq reveals Brg1-bound promoter-proximal and distal regions near genes essential for inner ear morphogenesis and cochlear sensory epithelium development. These findi...

Frontiers in Cell and Developmental Biology, 2019

F1000Research, 2019

Interaction with the world around us requires extracting meaningful signals to guide behavior. Ea... more 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 develop independently and must develop specific connections for proper sensory processing. In addition, the regulation of sensory map formation is independent of and prior to central target neuronal development in several maps. This review provides an overview of the current level of understanding of primary map formation of the six mammalian senses. Cell cycle exit, combined with incompletely understood molecules and their regulation, provides chemoaffinity-mediated primary maps that are further refined by activity. The interplay between cell cycle exit, molecular guidance, and activity-mediated refinement is the basis of dominance stripes...