Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:O76050 (neu)
 3,969 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The growth and differentiation of olfactory sensory neurons are regulated tightly. We had shown previously, by immunohistochemistry, that transforming growth factor-alpha (TGF-alpha) and epidermal growth factor (EGF) receptor are present in the olfactory epithelium of untreated adult rats and that TGF-alpha is a potent mitogen of olfactory epithelium in vitro. Expression of EGF receptor and TGF-alpha was detected primarily in horizontal basal cells and supporting cells but rarely in globose basal cells, which suggested that EGF receptor is not a likely candidate for the mitotic regulator of sensory neurons. In order to expand the search for candidate regulators, we have now examined other members of the EGF family of receptors and ligands. By utilizing reverse transcriptase-polymerase chain reaction (RT-PCR) methodology, we have detected the messenger RNA encoding the protein of the neu gene (p185neu) and Neu differentiation factor (NDF) isoforms in the olfactory mucosa. Immunohistochemical localization of p185neu and NDF indicates expression of these proteins in the olfactory epithelium of adult rats in regions where globose basal cells and immature sensory neurons are found, as well as in the ensheathing cells of the olfactory nerve. The presence of neu and NDF transcripts in the olfactory tissue and the localization of their encoded polypeptides to proliferative regions of the epithelium suggest involvement of these gene products in the regulated proliferation/differntiation of the sensory neurons.
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PMID:Expression of neu and Neu differentiation factor in the olfactory mucosa of rat. 901 Jul 26

The rat olfactory bulb is an exceptional CNS tissue. Unlike other areas of the brain, growing axons are able to enter the olfactory bulb and extend within this CNS environment throughout adult life. It appears that the glial cells of the olfactory system, known as olfactory bulb ensheathing cells (OBECs), may have an important role in this remarkable process of CNS neural regeneration. OBECs are unusual glial cells, possessing properties of both astrocytes and Schwann cells. In this study we show that astrocytes (in the form of astrocyte-conditioned medium; ACM) produce two critical regulatory functions for OBECs: mitogenic activity and a survival factor. Interestingly, the ACM-derived activity for OBECs appears to reside in a signalling protein(s) belonging to the neuregulin (NRG) family of growth factors, and specifically appears to coincide with one or more products of the nrg-1 gene. Our observations provide evidence for the following: recombinant human neu differentiation factors (NDFbeta1, -2 and -3) are mitogenic to OBECs; the activity in ACM can be neutralized by NDF antibodies; these same antibodies detect a 50-kDa, non-heparin binding protein in concentrated ACM; astrocytes express detectable nrg-1 transcripts; and OBECs express functional NRG receptors erbB2 and erbB4.
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PMID:Neuregulin is a mitogen and survival factor for olfactory bulb ensheathing cells and an isoform is produced by astrocytes. 1010 71

Neurogenic genes in the Notch receptor-mediated signaling pathway play important roles in neuronal cell fate specification as well as neuronal differentiation. The Drosophila neuralized gene is one of the neurogenic genes. We have cloned a mouse homolog of Drosophila neuralized, m-neu1, and found that the m-neu1 transcript is expressed in differentiated neurons. Mice deficient for m-neu1 are viable and morphologically normal, but exhibit specific defects in olfactory discrimination and hypersensitivity to ethanol. These findings reveal an essential role of m-neu1 in ensuring proper processing of certain information in the adult brain.
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PMID:Ethanol hypersensitivity and olfactory discrimination defect in mice lacking a homolog of Drosophila neuralized. 1148 56

PLU-1 is a novel breast cancer associated nuclear protein containing highly conserved domains including the PLU domain, putative DNA/chromatin binding motifs, and PHD/LAP domains. Here we report the cloning of the mouse homologue (Plu-1), and document its expression in adult tissues, mammary tumours and the embryo. The overall homology with human PLU-1 is 94% at the protein level, with almost 100% identity in the conserved domains, suggesting functional conservation. As with human PLU-1 the expression of Plu-1 in adult tissues is restricted, with high expression being seen only in testis, while expression in mammary tumours from c-neu transgenic mice is high. Plu-1 is also differentially expressed in the adult mammary gland. In the developing embryo Plu-1 is expressed in a temporally restricted fashion with tissue specific expression being limited to parts of the developing brain, whisker follicle, mammary bud, thymus, limbs, intervertebral disc, olfactory epithelium, teeth, eye, and stomach. The temporal and spatial expression patterns of the transcription factors Bf-1 and Pax9, recently found to bind to PLU-1 through the PLU domain overlap with Plu-1 expression during development. Thus Plu-1 appears to play an important role in mouse embryonic development which may involve interaction with Pax9 and Bf-1.
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PMID:Characterisation and developmental expression of mouse Plu-1, a homologue of a human nuclear protein (PLU-1) which is specifically up-regulated in breast cancer. 1261 14

PLU-1 is a novel breast cancer associated nuclear protein containing highly conserved domains including the PLU domain, putative DNA/chromatin binding motifs, and PHD/LAP domains. Here we report the cloning of the mouse homologue (Plu-1), and document its expression in adult tissues, mammary tumours and the embryo. The overall homology with human PLU-1 is 94% at the protein level, with almost 100% identity in the conserved domains, suggesting functional conservation. As with human PLU-1 the expression of Plu-1 in adult tissues is restricted, with high expression being seen only in testis, while expression in mammary tumours from c-neu transgenic mice is high. Plu-1 is also differentially expressed in the adult mammary gland. In the developing embryo Plu-1 is expressed in a temporally restricted fashion with tissue specific expression being limited to parts of the developing brain, whisker follicle, mammary bud, thymus, limbs, intervertebral disc, olfactory epithelium, teeth, eye, and stomach. The temporal and spatial expression patterns of the transcription factors Bf-1 and Pax9, recently found to bind to PLU-1 through the PLU domain overlap with Plu-1 expression during development. Thus Plu-1 appears to play an important role in mouse embryonic development which may involve interaction with Pax9 and Bf-1.
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PMID:Characterisation and developmental expression of mouse Plu-1, a homologue of a human nuclear protein (PLU-1) which is specifically up-regulated in breast cancer. 1451 92

Understanding how genotypic variation influences variation in brain structures and behavioral phenotypes represents a central challenge in behavioral genetics. In Drosophila melanogaster, the neuralized (neur) gene plays a key role in development of the nervous system. Different P-element insertional mutations of neur allow the development of viable and fertile adults with profoundly altered behavioral phenotypes that depend on the exact location of the inserted P element. The neur mutants exhibit reduced responsiveness to noxious olfactory and mechanosensory stimulation and increased aggression when limited food is presented after a period of food deprivation. These behavioral phenotypes are correlated with distinct structural changes in integrative centers in the brain, the mushroom bodies, and the ellipsoid body of the central complex. Transcriptional profiling of neur mutants revealed considerable overlap among ensembles of coregulated genes in the different mutants, but also distinct allele-specific differences. The diverse phenotypic effects arising from nearby P-element insertions in neur provide a new appreciation of the concept of allelic effects on phenotype, in which the wild type and null mutant are at the extreme ends of a continuum of pleiotropic allelic effects.
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PMID:Pleiotropic effects of Drosophila neuralized on complex behaviors and brain structure. 1856 39

The Dmrt (doublesex and mab-3 related transcription factor) genes encode a large family of evolutionarily conserved transcription factors whose function in sex specific differentiation has been well studied in all animal lineages. In vertebrates, their function is not restricted to the developing gonads. For example, Xenopus Dmrt4 is essential for neurogenesis in the olfactory system. Here we have isolated and characterized Xenopus Dmrt5 and found that it is coexpressed with Dmrt4 in the developing olfactory placodes. As Dmrt4, Dmrt5 is positively regulated in the ectoderm by neural inducers and negatively by proneural factors. Both Dmrt5 and Dmrt4 genes are also activated by the combined action of the transcription factor Otx2, broadly transcribed in the head ectoderm and of Notch signaling, activated in the anterior neural ridge. As for Dmrt4, knockdown of Dmrt5 impairs neurogenesis in the embryonic olfactory system and in neuralized animal caps. Conversely, its overexpression promotes neuronal differentiation in animal caps, a property that requires the conserved C-terminal DMA and DMB domains. We also found that the sea anenome Dmrt4/5 related gene NvDmrtb also induces neurogenesis in Xenopus animal caps and that conversely, its knockdown in Nematostella reduces elav-1 positive neurons. Together, our data identify Dmrt5 as a novel important regulator of neurogenesis whose function overlaps with that of Dmrt4 during Xenopus olfactory system development. They also suggest that Dmrt may have had a role in neurogenesis in the last common ancestor of cnidarians and bilaterians.
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PMID:The Xenopus doublesex-related gene Dmrt5 is required for olfactory placode neurogenesis. 2306 29

The extent to which epistasis affects the genetic architecture of complex traits is difficult to quantify, and identifying variants in natural populations with epistatic interactions is challenging. Previous studies in Drosophila implicated extensive epistasis between variants in genes that affect neural connectivity and contribute to natural variation in olfactory response to benzaldehyde. In this study, we implemented a powerful screen to quantify the extent of epistasis as well as identify candidate interacting variants using 203 inbred wild-derived lines with sequenced genomes of the Drosophila melanogaster Genetic Reference Panel (DGRP). We crossed the DGRP lines to P[GT1]-element insertion mutants in Sema-5c and neuralized (neur), two neurodevelopmental loci which affect olfactory behavior, and to their coisogenic wild-type control. We observed significant variation in olfactory responses to benzaldehyde among F1 genotypes and for the DGRP line by mutant genotype interactions for both loci, showing extensive nonadditive genetic variation. We performed genome-wide association analyses to identify the candidate modifier loci. None of these polymorphisms were in or near the focal genes; therefore, epistasis is the cause of the nonadditive genetic variance. Candidate genes could be placed in interaction networks. Several candidate modifiers are associated with neural development. Analyses of mutants of candidate epistatic partners with neur (merry-go-round (mgr), prospero (pros), CG10098, Alhambra (Alh) and CG12535) and Sema-5c (CG42540 and bruchpilot (brp)) showed aberrant olfactory responses compared with coisogenic controls. Thus, integrating genome-wide analyses of natural variants with mutations at defined genomic locations in a common coisogenic background can unmask specific epistatic modifiers of behavioral phenotypes.
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PMID:Epistatic partners of neurogenic genes modulate Drosophila olfactory behavior. 2667 46