scholarly journals Mechanosensory neuron regeneration in adult Drosophila

2019 ◽  
Author(s):  
Ismael Fernández-Hernández ◽  
Evan B. Marsh ◽  
Michael A. Bonaguidi
Keyword(s):  
Hair Cells ◽  
Lineage Tracing ◽  
Model Systems ◽  
Mechanosensory Neurons ◽  
Brain Circuitry ◽  
Summary Statement ◽  
Mechanosensory Hair Cells ◽  
Regenerative Therapies ◽  
First Time ◽  
Self Replication

ABSTRACTAuditory and vestibular mechanosensory hair cells do not regenerate following injury or aging in the adult mammalian inner ear, inducing irreversible hearing loss and balance disorders for millions of people. Research on model systems showing replacement of mechanosensory cells can provide mechanistic insights into developing new regenerative therapies. Here, we developed lineage tracing systems to reveal, for the first time, the generation of mechanosensory neurons in the Johnston’s Organ (JO) of intact adult Drosophila, which are the functional counterparts to hair cells in vertebrates. New JO neurons develop cilia, express an essential mechano-transducer gene and target central brain circuitry. Furthermore, we identified self-replication of JO neurons as an unexpected mechanism of neuronal plasticity, which is enhanced upon treatment with experimental and ototoxic compounds. Our findings introduce a new platform to expedite research about mechanisms and compounds mediating mechanosensory cell regeneration, with implications for hearing and balance restoration in humans.SUMMARY STATEMENTUsing refined lineage tracing and live imaging, we identified self-renewal of mechanosensory neurons in adult Drosophila, the functional counterparts to vertebrate hair cells, and their enhanced regeneration through pharmacological administration.

scholarly journals Mechanosensory neuron regeneration in adult Drosophila

Development ◽  
2021 ◽  
pp. dev.187534
Author(s):  
Ismael Fernández-Hernández ◽  
Evan B. Marsh ◽  
Michael A. Bonaguidi
Keyword(s):  
Hair Cells ◽  
Neuronal Plasticity ◽  
Lineage Tracing ◽  
Model Systems ◽  
Central Brain ◽  
Brain Circuitry ◽  
Mechanosensory Hair Cells ◽  
Regenerative Therapies ◽  
Self Replication ◽  
Adult Drosophila

Auditory and vestibular mechanosensory hair cells do not regenerate following injury or aging in the adult mammalian inner ear, inducing irreversible hearing loss and balance disorders for millions of people. Research on model systems showing replacement of mechanosensory cells can provide mechanistic insights into developing new regenerative therapies. Here, we developed lineage tracing systems to reveal the generation of mechanosensory neurons in the Johnston's Organ (JO) of intact adult Drosophila, which are the functional counterparts to hair cells in vertebrates. New JO neurons develop cilia and target central brain circuitry. Unexpectedly, mitotic recombination clones point to JO neuron self-replication as a likely source of neuronal plasticity. This mechanism is further enhanced upon treatment with experimental and ototoxic compounds. Our findings introduce a new platform to expedite research on mechanisms and compounds mediating mechanosensory cell regeneration, with nascent implications for hearing and balance restoration.

scholarly journals Lineage tracing of genome-edited alleles reveals high fidelity axolotl limb regeneration

eLife ◽  
2017 ◽  
Vol 6 ◽  
Author(s):  
Grant Parker Flowers ◽  
Lucas D Sanor ◽  
Craig M Crews
Keyword(s):  
Complex Structure ◽  
Limb Regeneration ◽  
Low Frequency ◽  
Lineage Tracing ◽  
High Fidelity ◽  
Cell Lineages ◽  
Ability To Regenerate ◽  
Unique Cell ◽  
Regenerative Therapies ◽  
First Time

Salamanders are unparalleled among tetrapods in their ability to regenerate many structures, including entire limbs, and the study of this ability may provide insights into human regenerative therapies. The complex structure of the limb poses challenges to the investigation of the cellular and molecular basis of its regeneration. Using CRISPR/Cas, we genetically labelled unique cell lineages within the developing axolotl embryo and tracked the frequency of each lineage within amputated and fully regenerated limbs. This allowed us, for the first time, to assess the contributions of multiple low frequency cell lineages to the regenerating limb at once. Our comparisons reveal that regenerated limbs are high fidelity replicas of the originals even after repeated amputations.

scholarly journals PINK1 deficiency impairs adult neurogenesis of dopaminergic neurons

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Sarah J. Brown ◽  
Ibrahim Boussaad ◽  
Javier Jarazo ◽  
Julia C. Fitzgerald ◽  
Paul Antony ◽  
...  
Keyword(s):  
Adult Neurogenesis ◽  
Neurodegenerative Disorders ◽  
Dopaminergic Neurons ◽  
Adult Life ◽  
Lineage Tracing ◽  
Model Systems ◽  
Wild Type ◽  
Therapeutic Approaches ◽  
Early Effect ◽  
Early Adult Life

AbstractRecent evidence suggests neurogenesis is on-going throughout life but the relevance of these findings for neurodegenerative disorders such as Parkinson’s disease (PD) is poorly understood. Biallelic PINK1 mutations cause early onset, Mendelian inherited PD. We studied the effect of PINK1 deficiency on adult neurogenesis of dopaminergic (DA) neurons in two complementary model systems. Zebrafish are a widely-used model to study neurogenesis in development and through adulthood. Using EdU analyses and lineage-tracing studies, we first demonstrate that a subset of ascending DA neurons and adjacent local-projecting DA neurons are each generated into adulthood in wild type zebrafish at a rate that decreases with age. Pink1-deficiency impedes DA neurogenesis in these populations, most significantly in early adult life. Pink1 already exerts an early effect on Th1+ progenitor cells rather than on differentiated DA neurons only. In addition, we investigate the effect of PINK1 deficiency in a human isogenic organoid model. Global neuronal differentiation in PINK1-deficient organoids and isogenic controls is similar, but PINK1-deficient organoids display impeded DA neurogenesis. The observation of impaired adult dopaminergic neurogenesis in Pink1 deficiency in two complementing model systems may have significant consequences for future therapeutic approaches in human PD patients with biallelic PINK1 mutations.

scholarly journals Translocation of silica nanospheres through giant unilamellar vesicles (GUVs) induced by a high frequency electromagnetic field

RSC Advances ◽  
2021 ◽  
Vol 11 (50) ◽  
pp. 31408-31420
Author(s):  
Palalle G. Tharushi Perera ◽  
Nevena Todorova ◽  
Zoltan Vilagosh ◽  
Olha Bazaka ◽  
The Hong Phong Nguyen ◽  
...  
Keyword(s):  
Electromagnetic Field ◽  
Membrane Permeability ◽  
Electromagnetic Fields ◽  
High Frequency ◽  
Model Systems ◽  
Membrane Model ◽  
Silica Nanospheres ◽  
Giant Unilamellar Vesicles ◽  
High Frequency Electromagnetic Field ◽  
First Time

Membrane model systems capable of mimicking live cell membranes were used for the first time in studying the effects arising from electromagnetic fields (EMFs) of 18 GHz where membrane permeability was observed following exposure.

scholarly journals Axodendritic versus axosomatic cochlear efferent termination is determined by afferent type in a hierarchical logic of circuit formation

2021 ◽  
Vol 7 (4) ◽  
pp. eabd8637
Author(s):  
Jemma L. Webber ◽  
John C. Clancy ◽  
Yingjie Zhou ◽  
Natalia Yraola ◽  
Kazuaki Homma ◽  
...  
Keyword(s):  
Hair Cells ◽  
Fiber Type ◽  
Afferent Fiber ◽  
Outer Hair Cells ◽  
Type I ◽  
Type Ii ◽  
Efferent Neurons ◽  
Distinct Pair ◽  
Mechanosensory Hair Cells ◽  
Circuit Formation

Hearing involves a stereotyped neural network communicating cochlea and brain. How this sensorineural circuit assembles is largely unknown. The cochlea houses two types of mechanosensory hair cells differing in function (sound transmission versus amplification) and location (inner versus outer compartments). Inner (IHCs) and outer hair cells (OHCs) are each innervated by a distinct pair of afferent and efferent neurons: IHCs are contacted by type I afferents receiving axodendritic efferent contacts; OHCs are contacted by type II afferents and axosomatically terminating efferents. Using an Insm1 mouse mutant with IHCs in the position of OHCs, we discover a hierarchical sequence of instructions in which first IHCs attract, and OHCs repel, type I afferents; second, type II afferents innervate hair cells not contacted by type I afferents; and last, afferent fiber type determines if and how efferents innervate, whether axodendritically on the afferent, axosomatically on the hair cell, or not at all.

scholarly journals B Cell Specific Knockdown of the Erythropoietin (EPO) Receptor Attenuates EPO-Induced Bone Loss in Mice

Blood ◽  
2019 ◽  
Vol 134 (Supplement_1) ◽  
pp. 939-939
Author(s):  
Albert Kolomansky ◽  
Naamit Deshet-Unger ◽  
Nathalie Ben-Califa ◽  
Zamzam Awida ◽  
Maria Ibrahim ◽  
...  
Keyword(s):  
B Cells ◽  
Bone Loss ◽  
B Cell ◽  
Trabecular Bone ◽  
Cell Lineage ◽  
Lineage Tracing ◽  
Trabecular Bone Loss ◽  
Β3 Integrin ◽  
First Time

Background and aims: Erythropoietin (EPO) is the key regulator of red blood cell production, commonly used in clinical practice to treat certain forms of anemia. Our studies and those of others have demonstrated that EPO administration induces substantial trabecular bone loss. We proposed that EPO-induced bone loss is partially mediated by subsets of bone marrow (BM) B cells that express EPO-R. Mechanistically, EPO upregulates the surface expression of RANKL by BM B cells and augments B cell-derived osteoclastogenesis in vitro. We showed that the latter is likely mediated by pro-B cells expressing the MCS-F receptor (CD115) and capable of transdifferentiation to osteoclasts (Abstract # 1007, EHA 2017). Here we address the role of B cell-specific EPO-R in EPO-induced bone loss (i.e. at supra-physiological EPO levels). Moreover, we demonstrate, for the first time, the occurrence of B cell-derived osteoclastogenesis in vivo, a finding of critical importance in the field of osteohematology. Methods: In order to trace the B cell lineage from its earliest precursors, we used the MB1-Cre mouse line combined with either the R26R-EYFP or the EPO-Rfl/fl mice for lineage tracing and B cell-specific EPO-R knockdown, respectively. Sequential fluorescence and light microscopy were used for the demonstration of B cell-derived osteoclastogenesis in vivo. Human recombinant EPO was administered in vivo at a dose of 180IU thrice weekly for two weeks. Immunophenotyping of BM B cell populations was assessed by multi-color flow cytometry. Results: Using female MB1-Cre; EPO-Rfl/fl (cKD) mice, we found that B cell-specific EPO-R knockdown attenuated the profound EPO-induced trabecular bone loss in the proximal part of the femoral distal metaphysis (proximal BV/TV 0.034±0.012% vs 0.007±0.003% in the cKD vs control mice, p<0.05, Figure 1). Remarkably, this effect was observed despite the fact that cKD mice attained higher hemoglobin levels following EPO treatment (21.1±0.1 mg/dL vs 20.4±0.2 mg/dL in the cKD vs control mice, p<0.05). An EPO-induced increase in CD115+ Pro-B cells was observed in EPO-treated control mice but was absent in the cKD mice. The latter finding correlates with the observed bone loss and indicates that the increased number of MCSF-R-expressing pro-B cells is dependent on B cell EPO-R. Supporting the osteoclastic potential of this specific B cell subpopulation is the fact that most of the CD115+ Pro-B cells also express β3 integrin (CD61) which is essential for osteoclast differentiation and function. Using the MB1-Cre;R26R-EYFP murine model for B cell lineage tracing, we could demonstrate that some of the TRAP+/ β3 integrin+ bone lining cells were also positive for EYFP (Figure 2). This demonstrates the B cell origin of some of the osteoclasts in vivo. Conclusions: Our work highlights B cells as an important extra-erythropoietic target of EPO-EPO-R signaling that regulates bone homeostasis and might also indirectly affect EPO-stimulated erythropoietic response. The relevance and the mechanisms of the latter phenomenon merits further investigation. Importantly, we present here, for the first time, histological evidence for B cell-derived osteoclastogenesis in vivo, thus opening novel research avenues. DN and YG Equal contribution Funded by the German Israel Foundation, Grant # 01021017 to YG, DN, MR and BW and by the Israel Science Foundation (ISF) Grant No. 343/17 to DN. Disclosures Mittelman: Novartis: Honoraria, Research Funding, Speakers Bureau.

Delta-Notch signalling and the patterning of sensory cell differentiation in the zebrafish ear: evidence from the mind bomb mutant

Development ◽  
1998 ◽  
Vol 125 (23) ◽  
pp. 4637-4644 ◽  
Author(s):  
C. Haddon ◽  
Y.J. Jiang ◽  
L. Smithers ◽  
J. Lewis
Keyword(s):  
Cell Differentiation ◽  
Lateral Inhibition ◽  
Hair Cells ◽  
Sensory Cell ◽  
Cell Types ◽  
Notch Signalling ◽  
Supporting Cells ◽  
Fine Grained ◽  
Mechanosensory Hair Cells ◽  
The Mind

Mechanosensory hair cells in the sensory patches of the vertebrate ear are interspersed among supporting cells, forming a fine-grained pattern of alternating cell types. Analogies with Drosophila mechanosensory bristle development suggest that this pattern could be generated through lateral inhibition mediated by Notch signalling. In the zebrafish ear rudiment, homologues of Notch are widely expressed, while the Delta homologues deltaA, deltaB and deltaD, coding for Notch ligands, are expressed in small numbers of cells in regions where hair cells are soon to differentiate. This suggests that the delta-expressing cells are nascent hair cells, in agreement with findings for Delta1 in the chick. According to the lateral inhibition hypothesis, the nascent hair cells, by expressing Delta protein, would inhibit their neighbours from becoming hair cells, forcing them to be supporting cells instead. The zebrafish mind bomb mutant has abnormalities in the central nervous system, somites, and elsewhere, diagnostic of a failure of Delta-Notch signalling: in the CNS, it shows a neurogenic phenotype accompanied by misregulated delta gene expression. Similar misregulation of delta; genes is seen in the ear, along with misregulation of a Serrate homologue, serrateB, coding for an alternative Notch ligand. Most dramatically, the sensory patches in the mind bomb ear consist solely of hair cells, which are produced in great excess and prematurely; at 36 hours post fertilization, there are more than ten times as many as normal, while supporting cells are absent. A twofold increase is seen in the number of otic neurons also. The findings are strong evidence that lateral inhibition mediated by Delta-Notch signalling controls the pattern of sensory cell differentiation in the ear.

scholarly journals Rheotaxis in Larval Zebrafish Is Mediated by Lateral Line Mechanosensory Hair Cells

PLoS ONE ◽  
2012 ◽  
Vol 7 (2) ◽  
pp. e29727 ◽  
Author(s):  
Arminda Suli ◽  
Glen M. Watson ◽  
Edwin W. Rubel ◽  
David W. Raible
Keyword(s):  
Lateral Line ◽  
Hair Cells ◽  
Larval Zebrafish ◽  
Mechanosensory Hair Cells

Leech Mechanosensation

2017 ◽  
Author(s):  
Brian D. Burrell
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Sensory Neurons ◽  
Receptive Fields ◽  
Model Systems ◽  
Sensory Cells ◽  
Mechanical Stimuli ◽  
Nociceptive Neurons ◽  
Mechanosensory Neurons ◽  
The Central Nervous System

The medicinal leech (Hirudo verbana) is an annelid (segmented worm) and one of the classic model systems in neuroscience. It has been used in research for over 50 years and was one of the first animals in which intracellular recordings of mechanosensory neurons were carried out. Remarkably, the leech has three main classes of mechanosensory neurons that exhibit many of the same properties found in vertebrates. The most sensitive of these neurons are the touch cells, which are rapidly adapting neurons that detect low-intensity mechanical stimuli. Next are the pressure cells, which are slow-adapting sensory neurons that respond to higher intensity, sustained mechanostimulation. Finally, there are nociceptive neurons, which have the highest threshold and respond to potentially damaging mechanostimuli, such as a pinch. As observed in mammals, the leech has separate mechanosensitive and polymodal nociceptors, the latter responding to mechanical, thermal, and chemical stimuli. The cell bodies for all three types of mechanosensitive neurons are found in the central nervous system where they are arranged as bilateral pairs. Each neuron extends processes to the skin where they form discrete receptive fields. In the touch and pressure cells, these receptive fields are arranged along the dorsal-ventral axis. For the mechano-only and polymodal nociceptive neurons, the peripheral receptive fields overlap with the mechano-only nociceptor, which also innervates the gut. The leech also has a type of mechanosensitive cell located in the periphery that responds to vibrations in the water and is used, in part, to detect potential prey nearby. In the central nervous system, the touch, pressure, and nociceptive cells all form synaptic connections with a variety of motor neurons, interneurons, and even each other, using glutamate as the neurotransmitter. Synaptic transmission by these cells can be modulated by a variety of activity-dependent processes as well as the influence of neuromodulatory transmitters, such as serotonin. The output of these sensory neurons can also be modulated by conduction block, a process in which action potentials fail to propagate to all the synaptic release sites, decreasing synaptic output. Activity in these sensory neurons leads to the initiation of a number of different motor behaviors involved in locomotion, such as swimming and crawling, as well as behaviors designed to recoil from aversive/noxious stimuli, such as local bending and shortening. In the case of local bending, the leech is able to bend in the appropriate direction away from the offending stimuli. It does so through a combination of which mechanosensory cell receptive fields have been activated and the relative activation of multiple sensory cells decoded by a layer of downstream interneurons.

Prestin Expression in Cochlea of Bats Using Different Echolocation Systems

2014 ◽  
Vol 620 ◽  
pp. 248-252
Author(s):  
Qi Jiu Li ◽  
Xian De Zhang ◽  
Ting Ting Xu ◽  
Jiang Xia Yin
Keyword(s):  
Hair Cells ◽  
High Frequency ◽  
Low Frequency ◽  
Motor Protein ◽  
Outer Hair Cells ◽  
Intracellular Potential ◽  
First Time ◽  
Unique Ability

Outer hair cells (OHCs) have a unique ability to contract and elongate in response to changes in intracellular potential, and Prestin is the motor protein of the cochlea of the OHCs. It is the first time to invest the Prestin expression in different bat species. To invest Prestin expression in different bat species, which have different frequency, we did the coronal sections’ staining of the cochlea using immunhistochemistry. Experiment was designed to determine if the high-frequency bats’ OHCs have more expression than the low-frequency bats’OHCs. We found that the expression in three species was similar and had no obvious difference. Though the study of bats Prestin evolution suggested that Prestin has accelerating evolution in echolocation bats with high frequency, our we showed that the Prestin expression has nothing to do with the frequency, and the Prestin expression in high-frequency bats and low-frequency bats is similar.

Sign in / Sign up

Export Citation Format

Share Document