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 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 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 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.

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

scholarly journals Larval zebrafish rapidly sense the water flow of a predator's strike

2009 ◽  
Vol 5 (4) ◽  
pp. 477-479 ◽  
Author(s):  
M.J. McHenry ◽  
K.E. Feitl ◽  
J.A. Strother ◽  
W.J. Van Trump
Keyword(s):  
Water Flow ◽  
Lateral Line ◽  
Hair Cells ◽  
Escape Response ◽  
Neuromuscular Control ◽  
Lateral Line System ◽  
Line System ◽  
Novel Device ◽  
Larval Fishes ◽  
Mechanosensory Hair Cells

Larval fishes have a remarkable ability to sense and evade the feeding strike of a predator fish with a rapid escape manoeuvre. Although the neuromuscular control of this behaviour is well studied, it is not clear what stimulus allows a larva to sense a predator. Here we show that this escape response is triggered by the water flow created during a predator's strike. Using a novel device, the impulse chamber, zebrafish ( Danio rerio ) larvae were exposed to this accelerating flow with high repeatability. Larvae responded to this stimulus with an escape response having a latency (mode=13–15 ms) that was fast enough to respond to predators. This flow was detected by the lateral line system, which includes mechanosensory hair cells within the skin. Pharmacologically ablating these cells caused the escape response to diminish, but then recover as the hair cells regenerated. These findings demonstrate that the lateral line system plays a role in predator evasion at this vulnerable stage of growth in fishes.

scholarly journals The cell biology of hearing

2010 ◽  
Vol 190 (1) ◽  
pp. 9-20 ◽  
Author(s):  
Martin Schwander ◽  
Bechara Kachar ◽  
Ulrich Müller
Keyword(s):  
Hair Cell ◽  
Inner Ear ◽  
Hair Cells ◽  
Cell Biology ◽  
Cell Development ◽  
Biological Mechanisms ◽  
Electrical Signals ◽  
Mechanosensory Hair Cells

Mammals have an astonishing ability to sense and discriminate sounds of different frequencies and intensities. Fundamental for this process are mechanosensory hair cells in the inner ear that convert sound-induced vibrations into electrical signals. The study of genes that are linked to deafness has provided insights into the cell biological mechanisms that control hair cell development and their function as mechanosensors.

scholarly journals A Single-Cell Atlas and Lineage Analysis of the Adult Drosophila Ovary

2019 ◽  
Author(s):  
Katja Rust ◽  
Lauren Byrnes ◽  
Kevin Shengyang Yu ◽  
Jason S. Park ◽  
Julie B. Sneddon ◽  
...  
Keyword(s):  
Stem Cells ◽  
Single Cell ◽  
Cell Types ◽  
Somatic Tissue ◽  
Lineage Tracing ◽  
Major Cell Type ◽  
Follicle Stem Cells ◽  
Drosophila Ovary ◽  
Adult Drosophila ◽  
Lineage Analysis

AbstractThe Drosophila ovary is a widely used model for germ cell and somatic tissue biology. We have used single-cell RNA-sequencing to build a comprehensive cell atlas of the adult Drosophila ovary containing unique transcriptional profiles for every major cell type in the ovary, including the germline and follicle stem cells. Using this atlas we identify novel tools for identification and manipulation of known and novel cell types and perform lineage tracing to test cellular relationships of previously unknown cell types. By this we discovered a new form of cellular plasticity in which inner germarial sheath cells convert to follicle stem cells in response to starvation.Graphical Abstract

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.

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