Degeneration of vestibular neurons in late embryogenesis of both heterozygous and homozygous BDNF null mutant mice

Development ◽  
1996 ◽  
Vol 122 (6) ◽  
pp. 1965-1973 ◽  
Author(s):  
L.M. Bianchi ◽  
J.C. Conover ◽  
B. Fritzsch ◽  
T. DeChiara ◽  
R.M. Lindsay ◽  
...  
Keyword(s):  
Time Course ◽  
Semicircular Canals ◽  
Vestibular Neurons ◽  
Neuronal Populations ◽  
Sensory Epithelia ◽  
Inner Ear Development ◽  
Late Embryogenesis ◽  
Vestibular Sensory Epithelia ◽  
Null Mutant Mice ◽  
Afferent Innervation

The generation of mice lacking specific neurotrophins permits evaluation of the trophic requirements of particular neuronal populations throughout development. In the present study, we examined the developing vestibulocochlear system to determine the time course of neurotrophin dependence and to determine whether competition occurred among developing cochlear or vestibular neurons for available amounts of either brain-derived neurotrophic factor (BDNF) or neurotrophin-4/5 (NT-4/5). Both cochlear and vestibular neurons were present in mice lacking NT-4/5. In contrast, vestibular neurons decreased in number beginning at mid-stages of inner ear development, in mice lacking BDNF. Early in development (E12.5-13), the size of the vestibular ganglion was normal in bdnf −/− mice. Decreased innervation to vestibular sensory epithelia was detected at E13.5-15, when progressive loss of all afferent innervation to the semicircular canals and reduced innervation to the utricle and saccule were observed. At E16.5-17, there was a reduction in the number of vestibular neurons in bdnf −/− mice. A further decrease in vestibular neurons was observed at P1 and P15. Compared to bdnf −/− mice, mice heterozygous for the BDNF null mutation (bdnf +/−) showed an intermediate decrease in the number of vestibular neurons from E16.5-P15. These data indicate a late developmental requirement of vestibular neurons for BDNF and suggest competition among these neurons for limited supplies of this factor.

The Scanning Electron Microscopic Observation of the Vestibular Sensory Epithelia

1969 ◽  
Vol 27 ◽  
pp. 40-41
Author(s):  
D.J. Lim ◽  
W.C. Lane
Keyword(s):  
Semicircular Canals ◽  
Electron Microscopic Observation ◽  
Gravitational Acceleration ◽  
Electron Microscopic ◽  
Sensory Epithelia ◽  
Scanning Electron Microscopic ◽  
Vestibular Sensory Epithelia ◽  
And Function ◽  
Sand Piles ◽  
Active Investigation

The morphology and function of the vestibular sensory organs has been extensively studied during the last decade with the advent of electron microscopy and electrophysiology. The opening of the space age also accelerated active investigation in this area, since this organ is responsible for the sensation of balance and of linear, angular and gravitational acceleration.The vestibular sense organs are formed by the saccule, utricle and three ampullae of the semicircular canals. The maculae (sacculi and utriculi) have otolithic membranes on the top of the sensory epithelia. The otolithic membrane is formed by a layer of thick gelatin and sand-piles of calcium carbonate crystals (Fig.l).

scholarly journals Regeneration of Vestibular Horizontal Semicircular Canal Afferents in Pigeons

2009 ◽  
Vol 102 (2) ◽  
pp. 1274-1286 ◽  
Author(s):  
Asim Haque ◽  
Mridha Zakir ◽  
J. David Dickman
Keyword(s):  
Time Course ◽  
Semicircular Canals ◽  
Behavioral Changes ◽  
Slow Time ◽  
Horizontal Semicircular Canal ◽  
Receptor Cells ◽  
Spontaneous Regeneration ◽  
Underlying Mechanisms ◽  
Afferent Innervation ◽  
Vestibular Receptor

Spontaneous regeneration of vestibular and auditory receptors and their innervating afferents in birds, reptiles, and amphibians are well known. Here, we produced a complete vestibular receptor loss and epithelial denervation using an ototoxic agent (streptomycin), after which we quantitatively characterized the afferent innervation of the horizontal semicircular canals following completed regeneration. We found that calyx, dimorph, and bouton afferents all regenerate in a manner the recapitulates the epithelial topography of normal birds, but over a slow time course. Similar to previous findings in the vestibular otolith maculae, regeneration occurs according to a three-stage temporal sequence. Bouton afferents regenerate during the first month of regeneration, followed by calyceal-bearing afferents in the second and third months. Calyx afferents were the last to regenerate in the final stage of recovery after 3 mo. We also found that regenerated afferents exhibited terminal morphologies that are significantly smaller, less complex, and innervate fewer receptor cells over smaller epithelial areas than those that develop through normative morphogenesis. These structural fiber changes in afferent innervation correlate to alterations in gaze responses during regeneration, although the exact underlying mechanisms responsible for behavioral changes remain unknown. Plasticity in central vestibular neurons processing motion information seem to be required to explain the observed morphologic and response adaptations observed in regenerating vestibular systems.

scholarly journals Cytochrome P450 26b1-mediated specification of vestibular striola and central zones is required for transient responses in linear acceleration

2019 ◽  
Author(s):  
Kazuya Ono ◽  
James Keller ◽  
Omar López Ramírez ◽  
Antonia González Garrido ◽  
Omid Zobeiri ◽  
...  
Keyword(s):  
Cytochrome P450 ◽  
Semicircular Canals ◽  
Linear Acceleration ◽  
Conditional Knockout ◽  
Otolith Organs ◽  
Vestibular Input ◽  
Balance Beam ◽  
Sensory Epithelia ◽  
Vestibular Sensory Epithelia ◽  
Vestibular Evoked Potentials

ABSTRACTEach vestibular sensory epithelia of the inner ear is divided into two zones, the striola and extrastriola in maculae of otolith organs and the central and peripheral zones in cristae of semicircular canals, that differ in morphology and physiology. We found that formation of striolar/central zones during embryogenesis requires Cytochrome P450 26b1 (Cyp26b1)-mediated degradation of retinoic acid (RA). In Cyp26b1 conditional knockout mice, the identities of the striolar/central zones were compromised, including abnormal innervating neurons and otoconia in otolith organs. Vestibular evoked potentials (VsEP) in response to jerk stimuli were largely absent. Vestibulo-ocular reflexes and standard motor performances such as forced swimming were unaffected, but mutants had head tremors and deficits in balance beam tests that were consistent with abnormal vestibular input. Thus, degradation of RA during embryogenesis is required for patterning highly specialized regions of the vestibular sensory epithelia that may provide acute feedback about head motion.

Nkx5-1 controls semicircular canal formation in the mouse inner ear

Development ◽  
1998 ◽  
Vol 125 (1) ◽  
pp. 33-39 ◽  
Author(s):  
T. Hadrys ◽  
T. Braun ◽  
S. Rinkwitz-Brandt ◽  
H.H. Arnold ◽  
E. Bober
Keyword(s):  
Homologous Recombination ◽  
Inner Ear ◽  
Homeobox Gene ◽  
Semicircular Canals ◽  
Otic Vesicle ◽  
Null Mutation ◽  
Complex Structures ◽  
Vestibular Organ ◽  
Inner Ear Development ◽  
Vestibular Organs

The inner ear develops from the otic vesicle, a one-cell-thick epithelium, which eventually transforms into highly complex structures including the sensory organs for balance (vestibulum) and hearing (cochlea). Several mouse inner ear mutations with hearing and balance defects have been described but for most the underlying genes have not been identified, for example, the genes controlling the development of the vestibular organs. Here, we report the inactivation of the homeobox gene, Nkx5-1, by homologous recombination in mice. This gene is expressed in vestibular structures throughout inner ear development. Mice carrying the Nkx5-1 null mutation exhibit behavioural abnormalities that resemble the typical hyperactivity and circling movements of the shaker/waltzer type mutants. The balance defect correlates with severe malformations of the vestibular organ in Nkx5-1(−/−) mutants, which fail to develop the semicircular canals. Nkx5-1 is the first ear-specific molecule identified to play a crucial role in the formation of the mammalian vestibular system.

On the Legacy of Genetically Altered Mouse Models to Explore Vestibular Function: Distribution of Vestibular Hair Cell Phenotypes in the Otoferlin-Null Mouse

2019 ◽  
Vol 128 (6_suppl) ◽  
pp. 125S-133S ◽  
Author(s):  
Terry J. Prins ◽  
Johnny J. Saldate ◽  
Gerald S. Berke ◽  
Larry F. Hoffman
Keyword(s):  
Hair Cell ◽  
Hair Cells ◽  
Vestibular Function ◽  
Null Mouse ◽  
Type I ◽  
Vestibular Hypofunction ◽  
Cellular Changes ◽  
Sensory Epithelia ◽  
Vestibular Sensory Epithelia ◽  
Cell Phenotypes

Objectives: Early in his career, David Lim recognized the scientific impact of genetically anomalous mice exhibiting otoconia agenesis as models of drastically compromised vestibular function. While these studies focused on the mutant pallid mouse, contemporary genetic tools have produced other models with engineered functional modifications. Lim and colleagues foresaw the need to analyze vestibular epithelia from pallid mice to verify the absence of downstream consequences that might be secondary to the altered load represented by otoconial agenesis. More generally, however, such comparisons also contribute to an understanding of the susceptibility of labyrinthine sensory epithelia to more widespread cellular changes associated with what may appear as isolated modifications. Methods: Our laboratory utilizes a model of vestibular hypofunction produced through genetic alteration, the otoferlin-null mouse, which has been shown to exhibit severely compromised stimulus-evoked neurotransmitter release in type I hair cells of the utricular striola. The present study, reminiscent of early investigations of Lim and colleagues that explored the utility of a genetically altered mouse to explore its utility as a model of vestibular hypofunction, endeavored to compare the expression of the hair cell marker oncomodulin in vestibular epithelia from wild-type and otoferlin-null mice. Results: We found that levels of oncomodulin expression were much greater in type I than type II hair cells, though were similar across the 3 genotypes examined (ie, including heterozygotes). Conclusion: These findings support the notion that modifications resulting in a specific component of vestibular hypofunction are not accompanied by widespread morphologic and cellular changes in the vestibular sensory epithelia.

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