New gene, nel, encoding a Mr 93 K protein with EGF‐like repeats is strongly expressed in neural tissues of early stage chick embryos

Matshuhashi, Sachiko; Noji, Sumihare; Koyama, Eiki; Myokai, Fumio; Ohuchi, Hideyo; Taniguchi, Shigehiko; Hori, Katsuji

doi:10.1002/aja.1002030209

Cited by 83 publications

(85 citation statements)

References 46 publications

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“…The Nel (strongly expressed in neural tissues and containing epidermal growth factor (EGF)-like domains) gene, encoding a protein containing six EGFlike domains, was first cloned from a chick embryoderived cDNA library in 1995 (Matsuhashi et al, 1995(Matsuhashi et al, , 1996. Later, Watanabe et al (1996) cloned a human Nel gene designated nel-like type1 (NELL1) from a human fetal-brain cDNA library in 1996.…”

Section: Introductionmentioning

confidence: 99%

Hypermethylation of the nel-like 1 gene is a common and early event and is associated with poor prognosis in early-stage esophageal adenocarcinoma

et al. 2007

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The nel-like1 (NELL1) gene maps to chromosome 11p15, which frequently undergoes loss of heterozygosity in esophageal adenocarcinoma (EAC). NELL1 promoter hypermethylation was examined by real-time methylationspecific polymerase chain reaction in 259 human esophageal tissues. Hypermethylation of this promoter showed highly discriminative receiver-operator characteristic curve profiles, clearly distinguishing esophageal squamous cell carcinoma (ESCC) and EAC from normal esophagus (NE) (Po0.001). NELL1 normalized methylation values were significantly higher in Barrett's metaplasia (BE), dysplastic Barrett's (D) and EAC than in NE (Po0.0000001). NELL1 hypermethylation frequency was zero in NE but increased early during neoplastic progression, to 41.7% in BE from patients with Barrett's alone, 52.5% in D and 47.8% in EAC. There was a significant correlation between NELL1 hypermethylation and BE segment length. Three (11.5%) of 26 ESCCs exhibited NELL1 hypermethylation. Survival correlated inversely with NELL1 hypermethylation in patients with stages I-II (P ¼ 0.0264) but not in stages III-IV (P ¼ 0.68) EAC. Treatment of KYSE220 ESCC and BIC EAC cells with 5-aza-2 0 -deoxycytidine reduced NELL1 methylation and increased NELL1 mRNA expression. NELL1 mRNA levels in EACs with an unmethylated NELL1 promoter were significantly higher than those in EACs with a methylated promoter (P ¼ 0.02). Promoter hypermethylation of NELL1 is a common, tissue-specific event in human EAC, occurs early during Barrett's-associated esophageal neoplastic progression, and is a potential biomarker of poor prognosis in early-stage EAC.

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Section: Introductionmentioning

confidence: 99%

Hypermethylation of the nel-like 1 gene is a common and early event and is associated with poor prognosis in early-stage esophageal adenocarcinoma

et al. 2007

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“…Of the 21 cDNAs identified in our screen as being more strongly expressed in the immature DRG than mature DRG, 9 differential screening patterns were validated by QPCR (Table 1). Of these cDNAs, one is a secreted glycoprotein: NELL2 (Matsuhashi et al, 1995;Nelson et al, 2002), one is a transcription factor: Y-box binding protein YB-1 (Kuwano et al, 2003), two are putative RING finger proteins: Goliath-1 and an EST corresponding to an unknown gene, one is a completely novel sequence, two correspond to ESTs that correspond to unknown genes, and one is Stathmin, a growth associated protein whose expression decreases in adult brain (Mori and Morii, 2002). As expected the majority of the randomly picked clones were not confirmed to be differentially expressed, while the clones selected on the basis of their differential signal intensities were validated.…”

Section: Confirmation Of Differential Gene Expression By Quantiative Pcrmentioning

confidence: 99%

Identification of genes regulating sensory neuron genesis and differentiation in the avian dorsal root ganglia

Nelson

Sadhu

Kasemeier

et al. 2004

Developmental Dynamics

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The dorsal root ganglia (DRG) derive from a population of migrating neural crest cells that coalesce laterally to the neural tube. As the DRG matures, discrete cell types emerge from a pool of differentiating progenitor cells. To identify genes that regulate sensory genesis and differentiation, we have designed screens to identify members from families of known regulatory molecules such as receptor tyrosine kinases, and generated full-length and subtractive cDNA libraries between immature and mature DRG for identifying novel genes not previously implicated in DRG development. Several genes were identified in these analyses that belong to important regulatory gene families. Quantitative PCR confirmed differential expression of candidate cDNAs identified from the subtraction/differential screening. In situ hybridization further validated dynamic expression of several cDNAs identified in our screens. Our results demonstrate the utility of combining specific and general screening approaches for isolating key regulatory genes involved in the genesis and differentiation of discrete cell types and tissues within the classic embryonic chick model system. Developmental Dynamics 229:618 -629, 2004.

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“…Interestingly, although it is expressed in all tissues during fetal development, expression of its mRNA is retained only in neural tissues after hatching (Matsuhashi et al, 1995). Two human and rat cDNAs were later isolated as NELL1 and NELL2 (nel-like genes), with 50% and 80% homology to nel Luce and Burrows, 1999;Watanabe et al, 1996).…”

Section: Introductionmentioning

confidence: 99%

“…NELL2 genes encode peptides of approximately 90 kDa that are highly glycosylated, resulting in a total monomeric size of approximately 130 kDa in COS-7 cells (Nelson et al, 2004). Secreted NELL2 has been suggested to have a putative function as a trophic factor (Matsuhashi et al, 1995;Watanabe et al, 1996). A study of the effect of recombinant rat NELL2 proteins on primary cultured neurons provided direct evidence that secreted NELL2 promotes the survival of primary neurons by decreasing mitogen-activated protein kinase activities (Aihara et al, 2003).…”

Section: Introductionmentioning

confidence: 99%

The Molecular Mechanism of NELL2 Movement and Secretion in Hippocampal Progenitor HiB5 Cells

Hwang

Kim

et al. 2013

Molecules and Cells

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Neural epidermal growth factor-like protein-like 2 (NELL2) is a secreted glycoprotein that is predominantly expressed in the nervous system, but little is known about the intracellular movement and secretion mechanism of this protein. By monitoring the localization and movements of enhanced green fluorescent protein (EGFP)-labeled NELL2 in living cultured hippocampal neuroprogenitor HiB5 cells, we determined the subcellular localization of NELL2 and its intracellular movement and secretion mechanism. Cterminal EGFP-fused NELL2 showed a typical expression pattern of secreted proteins, especially with respect to its localization in the endoplasmic reticulum, Golgi apparatus, and punctate structures. Vesicles containing NELL2 exhibited bidirectional movement in HiB5 cells. The majority of the vesicles (70.1%) moved in an anterograde direction with an average velocity of 0.454 μm/s, whereas some vesicles (28.7%) showed retrograde movement with an average velocity of 0.302 μm/s. The movement patterns of NELL2 vesicles were dependent upon the presence of microtubules in HiB5 cells. Anterograde movement of NELL2 did not lead to a detectable accumulation of NELL2 in the peripheral region of the cell, indicating that it was secreted into the culture medium. We also showed that the N-terminal 29 amino acids of NELL2 were important for secretion of this protein. Taken together, these results strongly suggest that the N-terminal region of NELL2 determines both the pattern of its intracellular expression and transport of NELL2 vesicles by high-velocity movement. Therefore, NELL2 may affect the cellular activity of cells in a paracrine or autocrine manner.

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New gene, nel, encoding a M_r 93 K protein with EGF‐like repeats is strongly expressed in neural tissues of early stage chick embryos

Abstract: A new gene, nel, was isolated from a 9-day-old chick embryonic cDNA library. The gene encodes a protein of 835 amino acids (93,407 M,

Cited by 83 publications

References 46 publications

Hypermethylation of the nel-like 1 gene is a common and early event and is associated with poor prognosis in early-stage esophageal adenocarcinoma

Hypermethylation of the nel-like 1 gene is a common and early event and is associated with poor prognosis in early-stage esophageal adenocarcinoma

Identification of genes regulating sensory neuron genesis and differentiation in the avian dorsal root ganglia

The Molecular Mechanism of NELL2 Movement and Secretion in Hippocampal Progenitor HiB5 Cells

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