title: Zfp423/OAZ mutation reveals the importance of Olf/EBF transcription activity in olfactory neuronal maturation.
abstract: Zfp423/OAZ, a multi-zinc finger protein, is proposed to participate in neuronal differentiation through interactions with the Olf/EBF (O/E) family of transcription factors and mediate extrinsic BMP signaling pathways. These activities are associated with distinct domains of the Olf/EBF-associated zinc finger (OAZ) protein. Sustained OAZ expression arrests olfactory sensory neurons (OSNs) at an immature state and alters olfactory receptor expression, but the mechanism remains elusive. We show here that constitutive expression of a C-terminal mutant OAZ (OAZΔC) in mice that selectively disrupts OAZ-O/E interaction while retaining other activities, exhibits apparently normal OSN differentiation. Additionally, interfering with potential BMP signaling pathways by inducible Follistatin expression in adult mice does not alter the neuronal lineage or differentiation status. Our results indicate that O/E-mediated processes are essential for the differentiation of OSNs and the establishment of a mature phenotype. BMP signaling pathways, if they are active in normal adult olfactory epithelium, may play a minor role in this tissue.
authors.affiliation: Center for Sensory Biology, Department of Molecular Biology and Genetics, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205, USA.
authors.forename: Yang A
authors.initials: YA
authors.lastname: Roby
authors.forename: Michael A
authors.initials: MA
authors.lastname: Bushey
authors.forename: Li E
authors.initials: LE
authors.lastname: Cheng
authors.forename: Heather M
authors.initials: HM
authors.lastname: Kulaga
authors.forename: Se-Jin
authors.initials: SJ
authors.lastname: Lee
authors.forename: Randall R
authors.initials: RR
authors.lastname: Reed
mesh_terms: D000818:Animals; D051792:Basic Helix-Loop-Helix Proteins / Q000502:physiology*; D019485:Bone Morphogenetic Proteins / Q000502:physiology; D019070:Cell Lineage; D004268:DNA-Binding Proteins / Q000737:chemistry / Q000235:genetics* / Q000502:physiology; D038681:Follistatin / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology; D018507:Gene Expression Regulation, Developmental; D017930:Genes, Reporter; D018257:Helix-Loop-Helix Motifs; D051379:Mice; D008810:Mice, Inbred C57BL; D055495:Neurogenesis / Q000235:genetics*; D009831:Olfactory Mucosa / Q000166:cytology; D018034:Olfactory Receptor Neurons / Q000166:cytology* / Q000378:metabolism; D010641:Phenotype; D017354:Point Mutation; D011485:Protein Binding; D025941:Protein Interaction Mapping; D017434:Protein Structure, Tertiary; D018035:Receptors, Odorant / Q000235:genetics / Q000502:physiology*; D011993:Recombinant Fusion Proteins / Q000502:physiology; D015398:Signal Transduction / Q000502:physiology; D013329:Structure-Activity Relationship; D014157:Transcription Factors / Q000737:chemistry / Q000235:genetics* / Q000502:physiology; D014158:Transcription, Genetic; D016335:Zinc Fingers / Q000235:genetics* / Q000502:physiology
chemical_list: D051792:Basic Helix-Loop-Helix Proteins; D019485:Bone Morphogenetic Proteins; D004268:DNA-Binding Proteins; D038681:Follistatin; D018035:Receptors, Odorant; D011993:Recombinant Fusion Proteins; D014157:Transcription Factors; C489922:Ebf2 protein, mouse; C484557:Ebfaz protein, mouse; C503233:FST protein, human