Nav2 is necessary for cranial nerve development and blood pressure regulation

McNeill, Elizabeth; Roos, Kenneth P.; Moechars, Dieder; Clagett‐Dame, Margaret

doi:10.1186/1749-8104-5-6

Cited by 40 publications

(30 citation statements)

References 62 publications

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“…NAV2 is involved in cerebellar and cranial nerve development, as well as in blood pressure regulation [52,53]. Recently, the NAV2 gene was found to be frequently fused to the WNT pathway gene TCF7L1 in colorectal carcinoma in a study by the Cancer Genome Atlas Network [54].…”

Section: Discussionmentioning

confidence: 99%

Gene expression signatures differentiate uterine endometrial stromal sarcoma from leiomyosarcoma

Davidson

Abeler

Hellesylt

et al. 2013

Gynecologic Oncology

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Objective Endometrial stromal sarcoma (ESS) and leiomyosarcoma (LMS) are the two most common uterine sarcomas, but both are rare tumors. The aim of the present study was to compare the global gene expression patterns of ESS and LMS. Methods Gene expression profiles of 7 ESS and 13 LMS were analyzed using the HumanRef-8 BeadChip from Illumina. Differentially expressed candidate genes were validated using quantitative real-time PCR and immunohistochemistry. Results Unsupervised hierarchical clustering using all 54,675 genes in the array separated ESS from LMS samples. We identified 549 unique probes that were significantly differentially expressed in the two malignancies by greater than 2-fold with 1% FDR cutoff using one-way ANOVA with Benjamini–Hochberg correction, of which 336 and 213 were overexpressed in ESS and LMS, respectively. Genes overexpressed in ESS included SLC7A10, EFNB3, CCND2, ECEL1, ITM2A, NPW, PLAG1 and GCGR. Genes overexpressed in LMS included CDKN2A, FABP3, TAGLN, JPH2, GEM, NAV2 and RAB23. The top 100 genes overexpressed in LMS included those coding for myosin light chain and caldesmon, but not the genes coding for desmin or actin. CD10 was not overexpressed in ESS. Results for selected genes were validated by quantitative real-time PCR and immunohistochemistry. Conclusions We present the first study in which gene expression profiling was shown to distinguish between ESS and LMS. The molecular signatures unique to each of these malignancies may aid in expanding the diagnostic battery for their differentiation, and may provide a molecular basis for prognostic studies and therapeutic target discovery.

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Section: Discussionmentioning

confidence: 99%

Gene expression signatures differentiate uterine endometrial stromal sarcoma from leiomyosarcoma

Davidson

Abeler

Hellesylt

et al. 2013

Gynecologic Oncology

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“…Neuron navigator 2 ( NAV2 , also known as r etinoic- a cid i nduced in n euro b lastoma-1; RAINB1, POMFIL1, HELAD1, unc53H2 ) functions in neurite outgrowth and axonal elongation in organisms ranging from Caenorhabditis elegans ( C. elegans ) to humans [1–4]. NAV2 was initially discovered as a gene induced by all- trans retinoic acid (atRA) in human neuroblastoma (SH-SY5Y) cells [5, 6].…”

Section: Introductionmentioning

confidence: 99%

14-3-3ε and NAV2 interact to regulate neurite outgrowth and axon elongation

Marzinke

Mavencamp

Duratinsky

et al. 2013

Archives of Biochemistry and Biophysics

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Neuron navigator 2 (NAV2) is required for all-trans retinoic acid (atRA) to induce neurite outgrowth in human neuroblastoma cells. Further, ectopic overexpression of full-length human NAV2 rescues an axonal elongation defect in the C. elegans unc-53 (NAV2 ortholog) mutant. Using a region of NAV2 that independently associates with the cytoskeleton as bait in a yeast-two-hybrid screen, 14-3-3ε was identified as a novel NAV2 interacting partner. Amino acids 761–936 of NAV2 are sufficient to confer a positive interaction with 14-3-3ε as evidenced by a two-hybrid screen and co-immunoprecipitation assay. Knockdown of 14-3-3ε leads to a decrease in atRA-mediated neurite outgrowth, similar to the elongation defects observed when NAV2 is depleted or mutated. Likewise, posterior lateral microtubule (PLM) defects in C. elegans fed unc-53 RNAi are similar to those fed ftt-2 (14-3-3 homolog) RNAi. The discovery of an interaction between NAV2 and 14-3-3ε could provide insight into the mechanism by which NAV2 participates in promoting cell migration and neuronal elongation.

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“…Several studies suggested that this gene plays an important role in cellular growth, migration, neuronal elongation and nervous system development (Coy et al, 2002;, Ishiguro et al, 2002; Maes et al, 2002; Merrill et al, 2002; Peeters et al, 2004; Clagett-Dame et al, 2006; McNeill et al, 2010; Marzinke et al, 2013). Furthermore, the NAV2 gene may be associated with episodic memory scores in AD (Yan et al, 2015).…”

Section: Discussionmentioning

confidence: 99%

“…However, the mechanism for the role of NAV2 in AD still remains unclear. An animal model has shown that the NAV2 gene plays an important role in shaping the development of the mammalian nervous system and is involved in blood pressure regulation (McNeill et al, 2010). One human study revealed that the AD associated SNP rs2702663 in the present study was previously associated with both plaque presence and area in Dominican families (Dong et al, 2012), implicating that NAV2 polymorphisms may be involved in the development of atherosclerosis.…”

Section: Discussionmentioning

confidence: 99%

“…38 exonsThe NAV2 gene was most highly expressed in brain and also in kidney, live, thyroid, mammary gland, and spinal cord (Coy et al, 2002; Maes et al, 2002; Merrill et al, 2002) and may play a role in cellular growth, migration, and nervous system development (Coy et al, 2002;, Ishiguro et al, 2002; Merrill et al, 2002; Peeters et al, 2004; Clagett-Dame et al, 2006; McNeill et al, 2010; Marzinke et al, 2013). Recently, NAV2 was found to be associated with episodic memory scores in AD (Yan et al, 2015).…”

Section: Introductionmentioning

confidence: 99%

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Family-based association analysis of NAV2 gene with the risk and age at onset of Alzheimer's disease

Wang

Liu

Chun

et al. 2017

Journal of Neuroimmunology

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The neuron navigator 2 (NAV2) gene is highly expressed in brain and involved in the nervous system development and may play a role in Alzheimer’s disease (AD). We aimed to investigate the associations of 317 single-nucleotide polymorphisms (SNPs) in the NAV2 gene with risk and age at onset (AAO) of AD using a family-based sample (1266 AD cases and 1279 healthy relatives). Association with the risk of AD was assessed using family-based association test -generalized estimating equations (FBAT- GEE) statistics while the association with AAO as a quantitative trait was evaluated using the FBAT-Wilcoxon statistic. Single marker analysis showed that 20 SNPs were significantly associated with AD (top SNP rs7112354 with p = 8.46×10−4) and 11 SNPs were associated with AAO (top SNP rs1354269 with p = 2.87×10−3). Interestingly, two SNPs rs17614100 and rs12364788 were associated with both the risk (p = 1.7×10−2 and 2.71×10−2; respectively) and AAO (p = 1.85×10−3 and 6.06×10−3; respectively). Haplotype analyses further supported the results of single marker analyses. The present study is the first study providing evidence of several genetic variants within the NAV2 gene influencing the risk and AAO of AD.

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Nav2 is necessary for cranial nerve development and blood pressure regulation

Cited by 40 publications

References 62 publications

Gene expression signatures differentiate uterine endometrial stromal sarcoma from leiomyosarcoma

Gene expression signatures differentiate uterine endometrial stromal sarcoma from leiomyosarcoma

14-3-3ε and NAV2 interact to regulate neurite outgrowth and axon elongation

Family-based association analysis of NAV2 gene with the risk and age at onset of Alzheimer's disease

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