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ISL1 and POU4F1 Directly Interact to Regulate the Differentiation and Survival of Inner Ear Sensory Neurons

ABSTRACT: Isl1 and Pou4f1 regulate a unique set of CVG gene cooperatively or individually. GO term analysis shows these genes are crucial for CVGs development. To estimate Isl1 and Pou4f1 directly or indirectly regulate these downstream genes and how they act to affect these genes, we performed the CUT&Tag of ISL1 and POU4F1 with the histone modifications, H3K4me3, H3K27ac and H3K27me3 in CVGs. The identity of the peaks were characterized and big chromatin profiles were obtained.

ORGANISM(S): Mus musculus

PROVIDER: GSE233840 | GEO | 2024/05/31

REPOSITORIES: GEO

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ISL1 and POU4F1 directly interact to regulate the differentiation and survival of inner ear sensory neurons

Project description:The inner ear sensory neurons play a pivotal role in auditory processing and balance control. Though significant progresses have been made, the underlying mechanisms controlling the differentiation and survival of the inner ear sensory neurons remain largely unknown. During development, ISL1 and POU4F transcription factors are co-expressed and are required for terminal differentiation, pathfinding, axon outgrowth and the survival of neurons in the central and peripheral nervous systems. However, little is understood about their functional relationship and regulatory mechanism in neural development. Here, we have knocked out Isl1 or Pou4f1 or both in mice of both sexes. In the absence of Isl1, the differentiation of cochleovestibular ganglion (CVG) neurons is disturbed and with that Isl1-deficient CVG neurons display defects in migration and axon pathfinding. Compound deletion of Isl1 and Pou4f1 causes a delay in CVG differentiation and results in a more severe CVG defect with a loss of nearly all of spiral ganglion neurons (SGNs). Moreover, ISL1 and POU4F1 interact directly in developing CVG neurons and act cooperatively as well as independently in regulating the expression of unique sets of CVG-specific genes crucial for CVG development and survival by binding to the cis-regulatory elements including the promoters of Fgf10, Pou4f2, and Epha5 and enhancers of Eya1 and Ntng2 These findings demonstrate that Isl1 and Pou4f1 are indispensable for CVG development and maintenance by acting epistatically to regulate genes essential for CVG development.

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ISL1 and POU4F1 directly interact to regulate the differentiation and survival of inner ear sensory neurons

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ISL1 and POU4F1 directly interact to regulate the differentiation and survival of inner ear sensory neurons

Project description:ISL1 and POU4F1 directly interact to regulate the differentiation and survival of inner ear sensory neurons

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ISL1 and POU4F1 Directly Interact to Regulate the Differentiation and Survival of Inner Ear Sensory Neurons

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