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Comprehensive analysis on the signaling pathway of Norrie disease protein (Ndp)

ABSTRACT: Comprehensive analysis on the signaling pathway of Norrie disease protein (Ndp)

PROVIDER: PRJNA725422 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR14332349_1.fastq.gz	Fastqsanger.gz
	SRR14332349_2.fastq.gz	Fastqsanger.gz
	SRR14332350_1.fastq.gz	Fastqsanger.gz
	SRR14332350_2.fastq.gz	Fastqsanger.gz
	SRR14332351_1.fastq.gz	Fastqsanger.gz

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Comprehensive analysis on the signaling pathway of Norrie disease protein (Ndp)

Project description:Mutations in the gene for Norrie disease protein (Ndp) cause syndromic deafness and blindness. We show that cochlear function in an Ndp knockout (KO) mouse deteriorated with age: at P3-P4, hair cells (HCs) showed progressive loss of Pou4f3 and Gfi1, key transcription factors for HC maturation, and Myo7a, a specialized myosin required for normal function of HC stereocilia. Loss of expression of these genes correlated to increasing HC loss and profound hearing loss by 2 months of age. We show that overexpression of the Ndp gene in neonatal supporting cells or, remarkably, upregulation of canonical Wnt signaling in HCs rescued HCs and cochlear function. We conclude that Ndp secreted from supporting cells orchestrates a transcription factor network for the maintenance and survival of HCs and that increasing the level of b-catenin, the intracellular effector of Wnt signaling, is sufficient to replace the functional requirement for Ndp in the cochlea.

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Gene expression in brain tissue from MOG-immunized wild-type or C57BL/6Je/e mice at disease maximum.

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