Cochlear Development; New Tools and Approaches

Kelley, Matthew W.

doi:10.3389/fcell.2022.884240

Cited by 9 publications

(9 citation statements)

References 175 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…New venues of research are constantly opening up. For example, single cell-RNA sequencing has revealed unexpected cell type heterogeneity within the cochlear epithelium (Kelley, 2022) or the auditory ganglion (Petitpré et al, 2018;Shrestha et al, 2018;Sun et al, 2018). It would be worthwhile to investigate the contribution of AS to this newly discovered transcriptomic diversity.…”

Section: Discussionmentioning

confidence: 99%

“…Conditional knockout studies and transcriptomic analyses have identified key transcription factors governing cochlear development (Elliott et al, 2021). Single cell RNA-sequencing techniques are now revealing transcriptomic heterogeneity with unprecedented resolution (Kelley, 2022). Transcriptional control, however, is only one aspect of genetic regulation.…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Alternative splicing in shaping the molecular landscape of the cochlea

Kim

Koo²,

Bok³

2023

Front. Cell Dev. Biol.

View full text Add to dashboard Cite

The cochlea is a complex organ comprising diverse cell types with highly specialized morphology and function. Until now, the molecular underpinnings of its specializations have mostly been studied from a transcriptional perspective, but accumulating evidence points to post-transcriptional regulation as a major source of molecular diversity. Alternative splicing is one of the most prevalent and well-characterized post-transcriptional regulatory mechanisms. Many molecules important for hearing, such as cadherin 23 or harmonin, undergo alternative splicing to produce functionally distinct isoforms. Some isoforms are expressed specifically in the cochlea, while some show differential expression across the various cochlear cell types and anatomical regions. Clinical phenotypes that arise from mutations affecting specific splice variants testify to the functional relevance of these isoforms. All these clues point to an essential role for alternative splicing in shaping the unique molecular landscape of the cochlea. Although the regulatory mechanisms controlling alternative splicing in the cochlea are poorly characterized, there are animal models with defective splicing regulators that demonstrate the importance of RNA-binding proteins in maintaining cochlear function and cell survival. Recent technological breakthroughs offer exciting prospects for overcoming some of the long-standing hurdles that have complicated the analysis of alternative splicing in the cochlea. Efforts toward this end will help clarify how the remarkable diversity of the cochlear transcriptome is both established and maintained.

show abstract

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Alternative splicing in shaping the molecular landscape of the cochlea

Kim

Koo²,

Bok³

2023

Front. Cell Dev. Biol.

View full text Add to dashboard Cite

show abstract

“…This strategy needs a more thorough and in-depth understanding of the molecular events that could eventually become novel therapeutic targets and/or diagnostic biomarkers of SNHL, to be exploited also in cochlear regeneration strategies. Thanks to the technological advancements in the field of molecular biology, recent progress has been made in identifying and characterizing novel genes involved in hearing loss [6], as well as new molecular mechanisms of cochlear development [7], degeneration and regeneration [8]. In this review, we aim to present cutting-edge molecular methodologies that have been used to investigate the genome, epigenome and transcriptome in cochlear research, as well as methods that could be employed in the next future 2 to expand our understanding in the field, such as the latest sophisticated single cell and spatial genomics, transcriptomics and epigenomics.…”

Section: Introductionmentioning

confidence: 99%

Advanced Omics Techniques for Understanding Cochlear Genome, Epigenome and Transcriptome in Health and Disease

Tisi,

Palaniappan,

Maccarrone

2023

Preprint

View full text Add to dashboard Cite

Advanced genomics, transcriptomics and epigenomics techniques are providing unprecedented insights into the understanding of the molecular underpinnings of the central nervous system, including the neuro-sensory cochlea of the inner ear. Here, we report for the first time a comprehensive and updated overview of the most advanced omics techniques for the study of nucleic acids, and their applications in cochlear research. We describe the available in vitro and in vivo models for hearing research, the principles of genomics, transcriptomics and epigenomics, alongside their most advanced technologies (like single cell omics and spatial omics), which allows to investigate the molecular events that occur at single cell resolution retaining the spatial information.

show abstract

“…Cellular-level investigation in the cochlea is mostly carried out on young mice (P1–2) before the temporal bone calcifies. However, mice are born deaf, and their hearing organ does not mature until the end of the second post-natal week [ 2 , 8 , 27 , 28 ]. In addition, its complex morphology makes it challenging to gain usable data from the sensory organ of hearing.…”

Section: Introductionmentioning

confidence: 99%

Ca2+ Dynamics of Gap Junction Coupled and Uncoupled Deiters’ Cells in the Organ of Corti in Hearing BALB/c Mice

Moysan,

Fazekas,

Fekete

et al. 2023

IJMS

View full text Add to dashboard Cite

ATP, as a paracrine signalling molecule, induces intracellular Ca2+ elevation via the activation of purinergic receptors on the surface of glia-like cochlear supporting cells. These cells, including the Deiters’ cells (DCs), are also coupled by gap junctions that allow the propagation of intercellular Ca2+ waves via diffusion of Ca2+ mobilising second messenger IP3 between neighbouring cells. We have compared the ATP-evoked Ca2+ transients and the effect of two different gap junction (GJ) blockers (octanol and carbenoxolone, CBX) on the Ca2+ transients in DCs located in the apical and middle turns of the hemicochlea preparation of BALB/c mice (P14–19). Octanol had no effect on Ca2+ signalling, while CBX inhibited the ATP response, more prominently in the middle turn. Based on astrocyte models and using our experimental results, we successfully simulated the Ca2+ dynamics in DCs in different cochlear regions. The mathematical model reliably described the Ca2+ transients in the DCs and suggested that the tonotopical differences could originate from differences in purinoceptor and Ca2+ pump expressions and in IP3–Ca2+ release mechanisms. The cochlear turn-dependent effect of CBX might be the result of the differing connexin isoform composition of GJs along the tonotopic axis. The contribution of IP3-mediated Ca2+ signalling inhibition by CBX cannot be excluded.

show abstract

Cochlear Development; New Tools and Approaches

Cited by 9 publications

References 175 publications

Alternative splicing in shaping the molecular landscape of the cochlea

Alternative splicing in shaping the molecular landscape of the cochlea

Advanced Omics Techniques for Understanding Cochlear Genome, Epigenome and Transcriptome in Health and Disease

Ca2+ Dynamics of Gap Junction Coupled and Uncoupled Deiters’ Cells in the Organ of Corti in Hearing BALB/c Mice

Contact Info

Product

Resources

About