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Zfp423/OAZ participates in a developmental switch during olfactory neurogenesis.

ABSTRACT: The coordination of gene expression is critical for cell differentiation and the subsequent establishment of tissue function. We show here that a multiple zinc finger transcription factor, Zfp423/OAZ, is transiently expressed in newly differentiating olfactory-receptor neurons (ORNs) and has a key role in coordinating the expression of immature and mature stage-specific genes. OAZ deletion in mice impairs aspects of ORN differentiation, particularly the patterns of axonal projection to the olfactory bulb. OAZ gain-of-function experiments show that sustained OAZ expression throughout ORN maturation arrests ORN development at an immature stage and alters OR gene expression. Importantly, reintroducing OAZ expression in mature ORNs suppresses mature marker expression and reactivates immature-specific markers. Together, these experiments suggest that OAZ participates in a developmental switch regulating the transition from differentiation to maturation in ORNs.

SUBMITTER: Cheng LE

PROVIDER: S-EPMC2866517 | biostudies-literature | 2007 May

REPOSITORIES: biostudies-literature

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Zfp423/OAZ participates in a developmental switch during olfactory neurogenesis.

Cheng Li E LE Reed Randall R RR

Neuron 20070501 4

The coordination of gene expression is critical for cell differentiation and the subsequent establishment of tissue function. We show here that a multiple zinc finger transcription factor, Zfp423/OAZ, is transiently expressed in newly differentiating olfactory-receptor neurons (ORNs) and has a key role in coordinating the expression of immature and mature stage-specific genes. OAZ deletion in mice impairs aspects of ORN differentiation, particularly the patterns of axonal projection to the olfac ...[more]

PMID: 17521568

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Project description:BackgroundAdult neurogenesis, fundamental for cellular homeostasis in the mammalian olfactory epithelium, requires major shifts in gene expression to produce mature olfactory sensory neurons (OSNs) from multipotent progenitor cells. To understand these dynamic events requires identifying not only the genes involved but also the cell types that express each gene. Only then can the interrelationships of the encoded proteins reveal the sequences of molecular events that control the plasticity of the adult olfactory epithelium.ResultsOf 4,057 differentially abundant mRNAs at 5 days after lesion-induced OSN replacement in adult mice, 2,334 were decreased mRNAs expressed by mature OSNs. Of the 1,723 increased mRNAs, many were expressed by cell types other than OSNs and encoded proteins involved in cell proliferation and transcriptional regulation, consistent with increased basal cell proliferation. Others encoded fatty acid metabolism and lysosomal proteins expressed by infiltrating macrophages that help scavenge debris from the apoptosis of mature OSNs. The mRNAs of immature OSNs behaved dichotomously, increasing if they supported early events in OSN differentiation (axon initiation, vesicular trafficking, cytoskeletal organization and focal adhesions) but decreasing if they supported homeostatic processes that carry over into mature OSNs (energy production, axon maintenance and protein catabolism). The complexity of shifts in gene expression responsible for converting basal cells into neurons was evident in the increased abundance of 203 transcriptional regulators expressed by basal cells and immature OSNs.ConclusionsMany of the molecular changes evoked during adult neurogenesis can now be ascribed to specific cellular events in the OSN cell lineage, thereby defining new stages in the development of these neurons. Most notably, the patterns of gene expression in immature OSNs changed in a characteristic fashion as these neurons differentiated. Initial patterns were consistent with the transition into a neuronal morphology (neuritogenesis) and later patterns with neuronal homeostasis. Overall, gene expression patterns during adult olfactory neurogenesis showed substantial similarity to those of embryonic brain.

Dataset Information

Zfp423/OAZ participates in a developmental switch during olfactory neurogenesis.

Publications

Zfp423/OAZ participates in a developmental switch during olfactory neurogenesis.

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