Ear neurosensory development Dotaz Zobrazit nápovědu
The role of Sox2 in neurosensory development is not yet fully understood. Using mice with conditional Islet1-cre mediated deletion of Sox2, we explored the function of Sox2 in neurosensory development in a model with limited cell type diversification, the inner ear. In Sox2 conditional mutants, neurons initially appear to form normally, whereas late- differentiating neurons of the cochlear apex never form. Variable numbers of hair cells differentiate in the utricle, saccule, and cochlear base but sensory epithelium formation is completely absent in the apex and all three cristae of the semicircular canal ampullae. Hair cells differentiate only in sensory epithelia known or proposed to have a lineage relationship of neurons and hair cells. All initially formed neurons lacking hair cell targets die by apoptosis days after they project toward non-existing epithelia. Therefore, late neuronal development depends directly on Sox2 for differentiation and on the survival of hair cells, possibly derived from common neurosensory precursors.
- MeSH
- delece genu MeSH
- myši transgenní MeSH
- myši MeSH
- neurogeneze fyziologie MeSH
- sakulus a utrikulus cytologie embryologie MeSH
- transkripční faktory SOXB1 genetika metabolismus MeSH
- vláskové buňky cytologie metabolismus MeSH
- zvířata MeSH
- Check Tag
- myši MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Research Support, N.I.H., Extramural MeSH
- Názvy látek
- Sox2 protein, mouse MeSH Prohlížeč
- transkripční faktory SOXB1 MeSH
SOX2 is essential for maintaining neurosensory stem cell properties, although its involvement in the early neurosensory development of cranial placodes remains unclear. To address this, we used Foxg1-Cre to conditionally delete Sox2 during eye, ear, and olfactory placode development. Foxg1-Cre mediated early deletion of Sox2 eradicates all olfactory placode development, and disrupts retinal development and invagination of the lens placode. In contrast to the lens and olfactory placodes, the ear placode invaginates and delaminates NEUROD1 positive neurons. Furthermore, we show that SOX2 is not necessary for early ear neurogenesis, since the early inner ear ganglion is formed with near normal central projections to the hindbrain and peripheral projections to the undifferentiated sensory epithelia of E11.5-12.5 ears. However, later stages of ear neurosensory development, in particular, the late forming auditory system, critically depend on the presence of SOX2. Our data establish distinct differences for SOX2 requirements among placodal sensory organs with similarities between olfactory and lens but not ear placode development, consistent with the unique neurosensory development and molecular properties of the ear.
- Klíčová slova
- Eye, Inner ear, Neuronal projections, Olfactory system, Placode development,
- MeSH
- apoptóza MeSH
- myši knockoutované MeSH
- myši MeSH
- neurogeneze * MeSH
- nosní sliznice embryologie metabolismus MeSH
- oční čočka embryologie metabolismus MeSH
- transkripční faktory SOXB1 genetika metabolismus MeSH
- vnitřní ucho cytologie embryologie metabolismus MeSH
- zvířata MeSH
- Check Tag
- myši MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Research Support, N.I.H., Extramural MeSH
- Názvy látek
- Sox2 protein, mouse MeSH Prohlížeč
- transkripční faktory SOXB1 MeSH
This review provides an up-to-date source of information on the primary auditory neurons or spiral ganglion neurons in the cochlea. These neurons transmit auditory information in the form of electric signals from sensory hair cells to the first auditory nuclei of the brain stem, the cochlear nuclei. Congenital and acquired neurosensory hearing loss affects millions of people worldwide. An increasing body of evidence suggest that the primary auditory neurons degenerate due to noise exposure and aging more readily than sensory cells, and thus, auditory neurons are a primary target for regenerative therapy. A better understanding of the development and function of these neurons is the ultimate goal for long-term maintenance, regeneration, and stem cell replacement therapy. In this review, we provide an overview of the key molecular factors responsible for the function and neurogenesis of the primary auditory neurons, as well as a brief introduction to stem cell research focused on the replacement and generation of auditory neurons.
- Klíčová slova
- auditory pathways, cochlea, genetic mutations, single-cell RNAseq, transcription factor,
- MeSH
- ganglion spirale embryologie fyziologie MeSH
- indukované pluripotentní kmenové buňky cytologie MeSH
- kochlea embryologie fyziologie MeSH
- lidé MeSH
- mozkový kmen MeSH
- mutace MeSH
- myši MeSH
- neurogeneze MeSH
- neurony fyziologie MeSH
- nucleus cochlearis embryologie fyziologie MeSH
- percepční nedoslýchavost patofyziologie MeSH
- regenerativní lékařství metody MeSH
- sekvence nukleotidů MeSH
- sluchové kmenové evokované potenciály MeSH
- vláskové buňky fyziologie MeSH
- vnitřní ucho embryologie fyziologie MeSH
- zvířata MeSH
- Check Tag
- lidé MeSH
- myši MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- přehledy MeSH
Sensorineural hearing loss is more common in patients with diabetes than in the control nondiabetic patients, and severity of hearing loss seemed to correlate with progression of disease. This may be due to microangiopathic disease in the inner ear. References for diabetic microangiopathy are presented. Sensorineural hearing loss can often be helped by hearing aids. During the last decade there have been significant developments in hearing aid technology. Progress began with the presentation of programmable hearing aids in the late 1980's. The first hearing aids with fully digital signal processing became commercially available in 1995. The hearing aid is programmable, which means that it can be adjusted individually by a hearing healthcare professional (hearing aid fitting at departments of phoniatrics and of audiology in our country). The article gives an outline of indications for hearing aids.
Ear development requires the transcription factors ATOH1 for hair cell differentiation and NEUROD1 for sensory neuron development. In addition, NEUROD1 negatively regulates Atoh1 gene expression. As we previously showed that deletion of the Neurod1 gene in the cochlea results in axon guidance defects and excessive peripheral innervation of the sensory epithelium, we hypothesized that some of the innervation defects may be a result of abnormalities in NEUROD1 and ATOH1 interactions. To characterize the interdependency of ATOH1 and NEUROD1 in inner ear development, we generated a new Atoh1/Neurod1 double null conditional deletion mutant. Through careful comparison of the effects of single Atoh1 or Neurod1 gene deletion with combined double Atoh1 and Neurod1 deletion, we demonstrate that NEUROD1-ATOH1 interactions are not important for the Neurod1 null innervation phenotype. We report that neurons lacking Neurod1 can innervate the flat epithelium without any sensory hair cells or supporting cells left after Atoh1 deletion, indicating that neurons with Neurod1 deletion do not require the presence of hair cells for axon growth. Moreover, transcriptome analysis identified genes encoding axon guidance and neurite growth molecules that are dysregulated in the Neurod1 deletion mutant. Taken together, we demonstrate that much of the projections of NEUROD1-deprived inner ear sensory neurons are regulated cell-autonomously.
- Klíčová slova
- Axon guidance, Central projections, Ear neurosensory development, Neuronal differentiation, bHLH genes,
- MeSH
- apoptóza genetika MeSH
- axony metabolismus MeSH
- biologické modely MeSH
- buněčná diferenciace genetika MeSH
- Cortiho orgán patologie MeSH
- delece genu MeSH
- epitel metabolismus MeSH
- ganglion spirale metabolismus MeSH
- mutace genetika MeSH
- myši knockoutované MeSH
- nervová vlákna metabolismus MeSH
- proteiny nervové tkáně genetika metabolismus MeSH
- regulace genové exprese MeSH
- stanovení celkové genové exprese MeSH
- transkripční faktory bHLH genetika metabolismus MeSH
- transkripční faktory SOXB1 metabolismus MeSH
- vláskové buňky metabolismus patologie ultrastruktura MeSH
- zvířata MeSH
- Check Tag
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- Názvy látek
- Atoh1 protein, mouse MeSH Prohlížeč
- Neurogenic differentiation factor 1 MeSH Prohlížeč
- proteiny nervové tkáně MeSH
- transkripční faktory bHLH MeSH
- transkripční faktory SOXB1 MeSH
We report a young woman with genetically confirmed Pendred syndrome and discuss the current therapeutic strategies of dyshormonogenetic goitre. A small diffuse thyroid enlargement developed during infancy and although substitution therapy with L-thyroxine was adequate, it progressed and underwent multinodular transformation. Cervical ultrasound at the age of 22 years demonstrated three solid nodules and fine-needle aspiration biopsy showed a finding typical of follicular adenoma. It is known that dyshormonogenetic goitres have a tendency to grow despite appropriate treatment with L-thyroxine. Management of a patient with Pendred syndrome requires careful follow-up and regular imaging of the thyroid. Although the therapeutic approach to dyshormonogenetic goitres is still controversial, in our patient we chose total thyroidectomy as the most advantageous method to prevent the development of malignancies that may arise more frequently from dyshormonogenetic goitres than from goitres of other aetiologies.
- MeSH
- dospělí MeSH
- lidé MeSH
- membránové transportní proteiny genetika MeSH
- mutace genetika MeSH
- percepční nedoslýchavost genetika MeSH
- syndrom MeSH
- thyreotropin krev MeSH
- thyroxin terapeutické užití MeSH
- transportéry síranu MeSH
- tyreoidektomie MeSH
- uzlová struma farmakoterapie genetika chirurgie MeSH
- vnitřní ucho abnormality MeSH
- Check Tag
- dospělí MeSH
- lidé MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- kazuistiky MeSH
- práce podpořená grantem MeSH
- Názvy látek
- membránové transportní proteiny MeSH
- SLC26A4 protein, human MeSH Prohlížeč
- thyreotropin MeSH
- thyroxin MeSH
- transportéry síranu MeSH
BACKGROUND: Pendred syndrome (OMIM274600) is one of the causes of congenital hypothyroidism due to thyroid dyshormonogenesis. It is an autosomal recessive disease classically characterized by dyshormonogenetic goitre and sensorineural deafness. It is caused by mutations in PDS/SLC26A4 gene encoding for pendrin--an anion transporter, mostly expressed in the thyroid gland and the inner ear. The thyroid impairment in Pendred syndrome develops only in 80% of affected individuals in form of a euthyroid or hypothyroid goitre, which is rarely present at birth, when it can be diagnosed by the neonatal screening for congenital hypothyroidism. The study was aimed to identify patients with Pendred syndrome among children with congenital or postnatal non-autoimmune hypothyroidism and subsequently confirm the diagnosis by finding mutations in the PDS/SLC26A4 gene. METHODS AND RESULTS: We examined two-hundred thirty-six Caucasians with hypothyroidism diagnosed by screening or developing later in childhood. The clinical diagnosis of Pendred syndrome was based on the laboratory and ultrasonographic signs of thyroid dyshormonogenesis (elevated TSH, low T4/fT4, goitre or normal thyroid volume) in association with sensorineural hearing loss. In subjects clinically diagnosed as Pendred syndrome, we sequenced all 21 exons of the PDS/SLC26A4 gene and their flanking intron-exon junctions. Among 236 children, nine fulfilled the diagnostic criteria of Pendred syndrome. In four, the diagnosis was confirmed by identification of mutations in the PDS/SLC26A4 gene, the remaining five patients were concluded phenocopies. CONCLUSIONS: Our study confirms the high phenotypic variability of thyroid impairment in Pendred syndrome and underlines the necessity of a molecular-genetic investigation for establishing the diagnosis in regard of the great number of phenocopies. However, from the endocrinologist's point of view, the genetic testing is only reasonable in patients with congenital hypothyroidism due to dyshormonogenesis in association with sever to profound sensorineural hearing loss.
- MeSH
- dítě MeSH
- dospělí MeSH
- fenotyp MeSH
- kojenec MeSH
- kongenitální hypotyreóza * diagnóza genetika MeSH
- lidé MeSH
- membránové transportní proteiny genetika MeSH
- mladiství MeSH
- mladý dospělý MeSH
- mutace MeSH
- percepční nedoslýchavost * genetika MeSH
- předškolní dítě MeSH
- rodokmen MeSH
- sekvenční analýza DNA MeSH
- struma * genetika MeSH
- syndrom MeSH
- transportéry síranu MeSH
- Check Tag
- dítě MeSH
- dospělí MeSH
- kojenec MeSH
- lidé MeSH
- mladiství MeSH
- mladý dospělý MeSH
- mužské pohlaví MeSH
- předškolní dítě MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- kazuistiky MeSH
- Názvy látek
- membránové transportní proteiny MeSH
- SLC26A4 protein, human MeSH Prohlížeč
- transportéry síranu MeSH
BACKGROUND: Mild to moderate hearing loss is common in patients with mucopolysaccharidosis (MPS) IVA. The hearing loss can be conductive, sensorineural, or mixed. However, in these patients, the mixed form is frequent, attributed to the combination of conductive and neurosensory elements, with slowly progressive evolution. Conductive hearing loss may be secondary to recurrent upper respiratory tract infections, serous otitis media, and deformities of the ear ossicles due to the accumulation of glycosaminoglycans (GAGs). Meanwhile, the sensorineural form is mainly attributed to the accumulation of GAGs in the auditory system. OBJECTIVE: The aim of this scoping review is to understand the extent and type of evidence in relation to the physiopathology, classification, epidemiology, and clinical management of hearing loss and the effect of therapy for hearing loss in patients with MPS IVA. METHODS: This scoping review includes participants across all genders and of no particular age group who are diagnosed with MPS IVA and develop hearing loss as a comorbidity. No exclusion criteria (country, language, or document type) will be applicable. The information sources will include experimental and quasi-experimental, analytical observational, observational, and qualitative studies. Unpublished literature will not be covered. Grey literature will be covered. A total of 2 independent reviewers will participate in the process of screening the literature, paper selection, and data extraction, and this process will be performed blindly. When all manuscripts have been selected, disagreements that arise between the 2 reviewers at each stage of the selection process will be resolved through discussion or with an additional reviewer. Results will be reported with descriptive statistics and information will be displayed in a diagrammatic or tabular manner, as explained in the JBI guidelines. RESULTS: The literature search was performed in November 2021 in MEDLINE, LILACS (Literatura Latino-Americana e do Caribe em Ciências da Saúde), the Cochrane Library, ScienceDirect, Google Scholar, and OpenGrey; a total of 780 results were retrieved. Completion of the review is expected in mid-2022. CONCLUSIONS: This scoping review will be the first to describe the extent of the information regarding the development of hearing loss in the MPS IVA population. The data gathered by this review may lead to an understanding of the grade of hearing loss in this population and allow for the assessment of possible interventions according to the disease pattern. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): PRR1-10.2196/32986.
- Klíčová slova
- Morquio syndrome, hearing loss, rare diseases, scoping review,
- Publikační typ
- časopisecké články MeSH
