Neuron Navigator: A Human Gene Family with Homology to unc-53, a Cell Guidance Gene from Caenorhabditis elegans

Maes, Tamara; Barceló, Anna; Buesa, Carlos

doi:10.1006/geno.2002.6799

Cited by 106 publications

(125 citation statements)

References 22 publications

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“…In neuronal cells, guidance molecules modulate growth cone motility through cytoskeletal changes (Guan and Rao, 2003). Both semaphorin 3C (SEMA3C) and neuron navigator 3 (NAV3) are involved in axonal guidance (Maes et al, 2002;Gonthier et al, 2007) where neuropilin-1 (NRP1) is a receptor for the semaphorins (He and TessierLavigne, 1997).…”

Section: Identification Of Genes Associated With Intrahepatic Metastamentioning

confidence: 99%

Identification of SOX4 target genes using phylogenetic footprinting-based prediction from expression microarrays suggests that overexpression of SOX4 potentiates metastasis in hepatocellular carcinoma

Yl¹,

et al. 2008

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A comprehensive microarray analysis of hepatocellular carcinoma (HCC) revealed distinct synexpression patterns during intrahepatic metastasis. Recent evidence has demonstrated that synexpression group member genes are likely to be regulated by master control gene(s). Here we investigate the functions and gene regulation of the transcription factor SOX4 in intrahepatic metastatic HCC. SOX4 is important in tumor metastasis as RNAi knockdown reduces tumor cell migration, invasion, in vivo tumorigenesis and metastasis. A multifaceted approach integrating gene profiling, binding site computation and empirical verification by chromatin immunoprecipitation and gene ablation refined the consensus SOX4 binding motif and identified 32 binding loci in 31 genes with high confidence. RNAi knockdown of two SOX4 target genes, neuropilin 1 and semaphorin 3C, drastically reduced cell migration activity in HCC cell lines suggesting that SOX4 exerts some of its action via regulation of these two downstream targets. The discovery of 31 previously unidentified targets expands our knowledge of how SOX4 modulates HCC progression and implies a range of novel SOX4 functions. This integrated approach sets a paradigm whereby a subset of member genes from a synexpression group can be regulated by one master control gene and this is exemplified by SOX4 and advanced HCC.

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Section: Identification Of Genes Associated With Intrahepatic Metastamentioning

confidence: 99%

Identification of SOX4 target genes using phylogenetic footprinting-based prediction from expression microarrays suggests that overexpression of SOX4 potentiates metastasis in hepatocellular carcinoma

Yl¹,

et al. 2008

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“…Among them, NAV3, alternatively named pore membrane and/or filament interacting like protein 1 (POMFIL1), was selected for further investigations because it is predominantly expressed in the nervous system (25). Although the precise biological function of NAV3 in the human brain remains unknown, a Caenorhabditis elegans gene named unc-53, highly homologous to NAV3, plays a key role in axon guidance (26). Although a previous study identified BACE1 as the most important target of miR-29a (16), we found BACE1 as one of miR-29a targets ranking 750th of 850 candidates on TargetScan and 197th of 326 candidates on PicTar.…”

Section: Mir-29a Decreased In Ad Brains Targets Nav3mentioning

confidence: 99%

MicroRNAs and Their Therapeutic Potential for Human Diseases: Aberrant MicroRNA Expression in Alzheimer’s Disease Brains

Satoh

2010

J Pharmacol Sci

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Abstract. MicroRNAs (miRNAs) are a group of small noncoding RNAs that regulate translational repression of multiple target mRNAs. The miRNAs in a whole cell regulate greater than 30% of all protein-coding genes. The vast majority of presently identified miRNAs are expressed in the brain in a spatially and temporally controlled manner. They play a key role in neuronal development, differentiation, and synaptic plasticity. However, at present, the pathological implications of deregulated miRNA expression in neurodegenerative diseases remain largely unknown. This review will briefly summarize recent studies that focus attention on aberrant miRNA expression in Alzheimer's disease brains.

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“…Unc-53 in C. elegans encodes a neural guidance factor required for axon elongation and cell migration (Maes et al, 2002;Schmidt et al, 2009;Stringham et al, 2002). In mammals, three unc-53 homolog genes exist: neuron navigator 1, 2 and 3 (Nav1, Nav2 and Nav3) (Maes et al, 2002).…”

Section: Introductionmentioning

confidence: 99%

“…In mammals, three unc-53 homolog genes exist: neuron navigator 1, 2 and 3 (Nav1, Nav2 and Nav3) (Maes et al, 2002). Both the unc-53 gene in C. elegans and Nav3 in rat and human have different isoforms (Maes et al, 2002;Peeters et al, 2004;Schmidt et al, 2009).…”

Section: Introductionmentioning

confidence: 99%

Neuron navigator 3a regulates liver organogenesis during zebrafish embryogenesis

et al. 2011

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SUMMARYEndodermal organogenesis requires a precise orchestration of cell fate specification and cell movements, collectively coordinating organ size and shape. In Caenorhabditis elegans, uncoordinated-53 (unc-53) encodes a neural guidance molecule that directs axonal growth. One of the vertebrate homologs of unc-53 is neuron navigator 3 (Nav3). Here, we identified a novel vertebrate neuron navigator 3 isoform in zebrafish, nav3a, and we provide genetic evidence in loss-and gain-of-function experiments showing its functional role in endodermal organogenesis during zebrafish embryogenesis. In zebrafish embryos, nav3a expression was initiated at 22 hpf in the gut endoderm and at 40 hpf expanded to the newly formed liver bud. Endodermal nav3a expression was controlled by Wnt2bb signaling and was independent of FGF and BMP signaling. Morpholino-mediated knockdown of nav3a resulted in a significantly reduced liver size, and impaired development of pancreas and swim bladder. In vivo time-lapse imaging of liver development in nav3a morphants revealed a failure of hepatoblast movement out from the gut endoderm during the liver budding stage, with hepatoblasts being retained in the intestinal endoderm. In hepatocytes in vitro, nav3a acts as a positive modulator of actin assembly in lamellipodia and filipodia extensions, allowing cellular movement. Knockdown of nav3a in vitro impeded hepatocyte movement. Endodermal-specific overexpression of nav3a in vivo resulted in additional ectopic endodermal budding beyond the normal liver and pancreatic budding sites. We conclude that nav3a is required for directing endodermal organogenesis involving coordination of endodermal cell behavior.

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Neuron Navigator: A Human Gene Family with Homology to unc-53, a Cell Guidance Gene from Caenorhabditis elegans

Cited by 106 publications

References 22 publications

Identification of SOX4 target genes using phylogenetic footprinting-based prediction from expression microarrays suggests that overexpression of SOX4 potentiates metastasis in hepatocellular carcinoma

Identification of SOX4 target genes using phylogenetic footprinting-based prediction from expression microarrays suggests that overexpression of SOX4 potentiates metastasis in hepatocellular carcinoma

MicroRNAs and Their Therapeutic Potential for Human Diseases: Aberrant MicroRNA Expression in Alzheimer’s Disease Brains

Neuron navigator 3a regulates liver organogenesis during zebrafish embryogenesis

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