Emx2Lineage Tracing Reveals Antecedent Patterns of Planar Polarity in the Mouse Inner Ear DOI Open Access

Ellison J. Goodrich,

Michael R. Deans

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2023, Volume and Issue: unknown

Published: Oct. 15, 2023

Abstract The planar polarized organization of vestibular hair cells in the utricle and saccule is unique because these inner ear sensory organs contain two groups with oppositely oriented stereociliary bundles that meet at a Line Polarity Reversal (LPR). This allows or to detect motions directed opposite directions, coordinated patterns neural innervation. EMX2 transcription factor only expressed by located on one side where it reverses orientation their thereby establishes position LPR. We generated Emx2 -CreERt2 transgenic mice for genetic lineage tracing demonstrate robust expression embryonic day 11.5 (E11.5), before cell specification, when nascent have not yet segregated from common prosensory domain. All derived E11.5 are restricted LPR mature indicating an antecedent may be established stage. Consistent this, Dreher mutant mice, fail segregate, labels continuous field distributed along fused utricular-saccular-cochlear organ. Altogether observations reveal origin developing domain, presence absence defines progenitor distinct lineages include bundles.

Language: Английский

TMC function, dysfunction, and restoration in mouse vestibular organs DOI Creative Commons

Evan M. Ratzan,

John Lee,

Margot A. Madison

et al.

Frontiers in Neurology, Journal Year: 2024, Volume and Issue: 15

Published: April 4, 2024

Tmc1 and Tmc2 are essential pore-forming subunits of mechanosensory transduction channels localized to the tips stereovilli in auditory vestibular hair cells inner ear. To investigate expression function organs, we used quantitative polymerase chain reaction (qPCR), fluorescence situ hybridization – hairpin (FISH-HCR), immunostaining, FM1-43 uptake measured evoked potentials (VsEPs) ocular reflexes (VORs). We found that showed dynamic developmental changes, differences regional patterns, overall levels which differed between utricle saccule. These underlying changes contributed unanticipated phenotypic loss VsEPs VORs KO mice. In contrast, mice retained despite calcium buffering protein calretinin, a characteristic biomarker mature striolar calyx-only afferents. Lastly, neonatal gene replacement therapy is sufficient restore VsEP for up six months post-injection.

Language: Английский

Citations

5
Not a hair out of place: Polarizing and orienting sensory hair cells DOI
Katie S. Kindt, Basile Tarchini

Current topics in developmental biology/Current Topics in Developmental Biology, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 1, 2025

Language: Английский

Citations

0
Emx2 lineage tracing reveals antecedent patterns of planar polarity in the mouse inner ear DOI Creative Commons

Ellison J. Goodrich,

Michael R. Deans

Development, Journal Year: 2024, Volume and Issue: 151(10)

Published: April 29, 2024

The planar polarized organization of hair cells in the vestibular maculae is unique because these sensory organs contain two groups with oppositely oriented stereociliary bundles that meet at a line polarity reversal (LPR). EMX2 transcription factor expressed by one cell group reverses orientation their bundles, thereby forming LPR. We generated Emx2-CreERt2 transgenic mice for genetic lineage tracing and demonstrate Emx2 expression before specification when nascent utricle saccule constitute continuous prosensory domain. Precursors labeled this stage give rise to located along side LPR mature or saccule, indicating boundary first established Consistent this, Dreher mutants, where fail segregate, labels field fused utriculo-saccular-cochlear organ. These observations reveal positioning pre-determined developing domain, defines lineages bundles.

Language: Английский

Citations

2
Inhibitory G proteins play multiple roles to polarize sensory hair cell morphogenesis DOI Creative Commons
Amandine Jarysta, Abigail L. D. Tadenev, Matthew Day

et al.

eLife, Journal Year: 2023, Volume and Issue: 12

Published: July 18, 2023

Inhibitory G alpha (GNAI or Gαi) proteins are critical for the polarized morphogenesis of sensory hair cells and hearing. The extent nature their actual contributions remains unclear, however, as previous studies did not investigate all GNAI included non-physiological approaches. Pertussis toxin can downregulate functionally redundant GNAI1, GNAI2, GNAI3, GNAO proteins, but may also induce unrelated defects. Here, we directly systematically determine role(s) each individual protein in mouse auditory cells. GNAI2 GNAI3 similarly at cell apex with binding partner signaling modulator 2 (GPSM2), whereas GNAI1 detected. In Gnai3 mutants, progressively fails to fully occupy sub-cellular compartments where is missing. contrast, compensate loss essential bundle function. Simultaneous inactivation Gnai2 recapitulates first time two distinct types defects only observed so far pertussis toxin: (1) a delay failure basal body migrate off-center prospective cells, (2) reversal orientation some types. We conclude that break planar symmetry orient properly before GNAI2/3 regulate GPSM2.

Language: Английский

Citations

6
Inhibitory G proteins play multiple roles to polarize sensory hair cell morphogenesis DOI Creative Commons
Amandine Jarysta, Abigail L. D. Tadenev, Matthew Day

et al.

eLife, Journal Year: 2024, Volume and Issue: 12

Published: April 23, 2024

Inhibitory G alpha (GNAI or Gαi) proteins are critical for the polarized morphogenesis of sensory hair cells and hearing. The extent nature their actual contributions remains unclear, however, as previous studies did not investigate all GNAI included non-physiological approaches. Pertussis toxin can downregulate functionally redundant GNAI1, GNAI2, GNAI3, GNAO proteins, but may also induce unrelated defects. Here, we directly systematically determine role(s) each individual protein in mouse auditory cells. GNAI2 GNAI3 similarly at cell apex with binding partner signaling modulator 2 (GPSM2), whereas GNAI1 detected. In Gnai3 mutants, progressively fails to fully occupy sub-cellular compartments where is missing. contrast, compensate loss essential bundle function. Simultaneous inactivation Gnai2 recapitulates first time two distinct types defects only observed so far pertussis toxin: (1) a delay failure basal body migrate off-center prospective cells, (2) reversal orientation some types. We conclude that break planar symmetry orient properly before GNAI2/3 regulate GPSM2.

Language: Английский

Citations

1
Comparative biology of the amniote vestibular utricle DOI Creative Commons
Marcela Lipovsek

Hearing Research, Journal Year: 2024, Volume and Issue: 448, P. 109035 - 109035

Published: May 19, 2024

The sensory epithelia of the auditory and vestibular systems vertebrates have shared developmental evolutionary histories. However, while show great variation across vertebrates, appear seemingly more conserved. An exploration current knowledge comparative biology amniote utricle, a epithelium that senses linear acceleration, shows interesting instances variability between birds mammals. distribution hair cell types, position line bundle polarity reversal properties supporting cells marked differences, likely impacting function regeneration potential.

Language: Английский

Citations

1
Effects of aging on otolith morphology and functions in mice DOI Creative Commons

Keita Ueda,

Takao Imai, Taeko Ito

et al.

Frontiers in Neuroscience, Journal Year: 2024, Volume and Issue: 18

Published: Oct. 16, 2024

Background Increased fall risk caused by vestibular system impairment is a significant problem associated with aging. A vestibule composed of linear acceleration-sensing otoliths and rotation-sensing semicircular canals. Otoliths, utricle saccule, detect accelerations. Otolithic organs partially play role in falls due to Aging possibly changes the morphology functions otoliths. However, specific associations between aging otolith remain unknown. Therefore, this study aimed clarify these mice. Methods Young C56BL/6 N (8 week old) old (108–117 weeks mice were used micro-computed tomography (μCT) experiment for morphological analysis acceleration functional analysis. middle-aged (50 electron microscopy experiments Results μCT revealed no differences volume ( p = 0.11) but density 0.001) young structure striola at center (μCT; 0.029, microscopy; 0.017). Significant also observed amplitude eye movement during vestibulo-ocular reflex induced (maximum stimulation 1.3G [ 0.014]; maximum 0.7G 0.015]), indicating that function was worse than Discussion This demonstrated decline age age-related changes. Specifically, when decreased, inertial force acting on hair cells collapsed, cross-striolar inhibition thereby causing overall function.

Language: Английский

Citations

1
Stem and progenitor cell proliferation are independently regulated by cell type-specific cyclinD genes DOI Creative Commons
Mark E. Lush, Ya-Yin Tsai, Shiyuan Chen

et al.

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2024, Volume and Issue: unknown

Published: Oct. 22, 2024

Regeneration and homeostatic turnover of solid tissues depend on the proliferation symmetrically dividing adult stem cells, which either remain cells or differentiate based their niche position. Here we demonstrate that in zebrafish lateral line sensory organs, progenitor cell are independently regulated by two

Language: Английский

Citations

0
Inhibitory G proteins play multiple roles to polarize sensory hair cell morphogenesis DOI Open Access
Amandine Jarysta, Abigail L. D. Tadenev, Matthew Day

et al.

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2023, Volume and Issue: unknown

Published: May 25, 2023

Inhibitory G alpha (GNAI or Gαi) proteins are critical for the polarized morphogenesis of sensory hair cells and hearing. The extent nature their actual contributions remains unclear, however, as previous studies did not investigate all GNAI included non-physiological approaches. Pertussis toxin can downregulate functionally redundant GNAI1, GNAI2, GNAI3 GNAO proteins, but may also induce unrelated defects. Here we directly systematically determine role(s) each individual protein in mouse auditory cells. GNAI2 similarly at cell apex with binding partner GPSM2, whereas GNAI1 detected. In

Language: Английский

Citations

0
Emx2Lineage Tracing Reveals Antecedent Patterns of Planar Polarity in the Mouse Inner Ear DOI Open Access

Ellison J. Goodrich,

Michael R. Deans

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2023, Volume and Issue: unknown

Published: Oct. 15, 2023

Abstract The planar polarized organization of vestibular hair cells in the utricle and saccule is unique because these inner ear sensory organs contain two groups with oppositely oriented stereociliary bundles that meet at a Line Polarity Reversal (LPR). This allows or to detect motions directed opposite directions, coordinated patterns neural innervation. EMX2 transcription factor only expressed by located on one side where it reverses orientation their thereby establishes position LPR. We generated Emx2 -CreERt2 transgenic mice for genetic lineage tracing demonstrate robust expression embryonic day 11.5 (E11.5), before cell specification, when nascent have not yet segregated from common prosensory domain. All derived E11.5 are restricted LPR mature indicating an antecedent may be established stage. Consistent this, Dreher mutant mice, fail segregate, labels continuous field distributed along fused utricular-saccular-cochlear organ. Altogether observations reveal origin developing domain, presence absence defines progenitor distinct lineages include bundles.

Language: Английский

Citations

0