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Position Specific Alternative Splicing and Gene Expression Profiles along the Tonotopic Axis of Chick Cochlea

ABSTRACT: Position Specific Alternative Splicing and Gene Expression Profiles along the Tonotopic Axis of Chick Cochlea

PROVIDER: PRJNA736607 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR14777101_1.fastq.gz	Fastqsanger.gz
	SRR14777101_2.fastq.gz	Fastqsanger.gz
	SRR14777102_1.fastq.gz	Fastqsanger.gz
	SRR14777102_2.fastq.gz	Fastqsanger.gz
	SRR14777103_1.fastq.gz	Fastqsanger.gz

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Position Specific Alternative Splicing and Gene Expression Profiles along the Tonotopic Axis of Chick Cochlea

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Project description:The cochlear duct is tonotopically organized, such that the basal cochlea responds more sensitively to high frequency sounds and the apical cochlea to low frequency sounds. In effort to understand how the tonotopic organization is established in mammals, we searched for genes that are differentially expressed along the tonotopic axis during neonatal development. Eighty temporal bones were dissected from C57BL/6 mice at P0 and P8. The cochlear tissues were divided into three equal pieces representing the basal, middle and apical turns, and pooled separately. Six total RNA from the pooled samples were applied to 6 GeneChips.

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Project description:In the mammalian auditory system, frequency discrimination depends on numerous morphological and physiological properties of the organ of Corti that gradually change along the longitudinal (tonotopic) axis of the organ. For example, the basilar membrane stiffness changes tonotopically, thus affecting the tuning properties of individual hair cells. At the molecular level, those frequency-specific characteristics are mirrored by gene expression gradients; however, the molecular mechanisms controlling tonotopic gene expression in the mouse cochlea remain elusive. Through analyzing scRNA-seq data from two developmental time points, we predicted that morphogens, rather than a timing-associated mechanism, confer spatial identity in the cochlea. Subsequently, we reconstructed the developing cochlea in 3D space from scRNA-seq data to investigate the molecular pathways mediating tonotopic information. The retinoic acid and sonic hedgehog pathways were found to form opposing tonotopic gradients, and functional interrogation using mouse cochlear explants suggested that both pathways jointly specify the tonotopic axis during development.

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Position Specific Alternative Splicing and Gene Expression Profiles Along the Tonotopic Axis of Chick Cochlea.

Project description:Alternative splicing (AS) refers to the production of multiple mRNA isoforms from a single gene due to alternative selection of exons or splice sites during pre-mRNA splicing. It is a primary mechanism of gene regulation in higher eukaryotes and significantly expands the functional complexity of eukaryotic organisms, contributing to animal development and disease. Recent studies have shown that AS also influences functional diversity by affecting the transcriptomic and proteomic profiles in a position-dependent manner in a single organ. The peripheral hearing organ, the cochlea, is organized to detect sounds at different frequencies depending on its location along the longitudinal axis. This unique functional configuration, the tonotopy, is known to be facilitated by differential gene expression along the cochlear duct. We profiled transcriptome-wide gene expression and AS changes that occur within the different positions of chick cochlea. These analyses revealed distinct gene expression profiles and AS, including a splicing program that is unique to tonotopy. Changes in the expression of splicing factors PTBP3, ESRP1, and ESRP2 were demonstrated to contribute to position-specific AS. RNA-binding motif enrichment analysis near alternatively spliced exons provided further insight into the combinatorial regulation of AS at different positions by different RNA-binding proteins. These data, along with gene ontology (GO) analysis, represent a comprehensive analysis of the dynamic regulation of AS at different positions in chick cochlea.

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Mus musculus

Project description:Gene expression profiles along the tonotopic axis of the mouse cochlea during neonatal development

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