Cloning and Characterization of Two Novel Human cDNAs (NELL1 and NELL2) Encoding Proteins with Six EGF-like Repeats

Watanabe, Takeshi; Katagiri, Toyomasa; Suzuki, Mikio; Shimizu, Fumio; Fujiwara, Tsutomu; Kanemoto, Naohide; Nakamura, Yusuke; Hirai, Yoshikatsu; Maekawa, Hiroumi; Takáhashi, Eiichi

doi:10.1006/geno.1996.0628

Cited by 122 publications

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“…For example, in ongoing work we have evidence that NELL2 induces neuronal differentiation within the DRG (Nelson et al, submitted). NELL2 belongs to an intriguing class of proteins that contain EGF-like domains (Watanabe et al, 1996;Engel, 1989;Davis, 1990), including amongst others, Notch and its ligands Delta/ Serrate/Lag (DSL), the Neuregulin (NRG) family of ligands, and the SLIT family of ligands. NELL2 is a secreted glycoprotein and belongs to the Laminin G/N-terminus Thrombospondin 1 (N-TSP1)/Pentraxin gene superfamily (Beckmann et al, 1998).…”

Section: Discussionmentioning

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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Section: Discussionmentioning

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 N-terminal 29 amino acids of NELL2 are responsible for secretion Although previous studies deduced that NELL2 contains several functional domains in its amino acid sequence Watanabe et al, 1996) (Fig. 4A), which domain is critical for NELL2 secretion has not been characterized.…”

Section: Microtubule-dependent Transport Of Nell2-egfp Vesiclesmentioning

confidence: 99%

“…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). Neural tissue-specific expression of NELL2 has been reported in developing and post-natal rats (Kim et al, 2002;Nelson et al, 2004;Oyasu et al, 2000) and humans (Watanabe et al, 1996).…”

Section: Introductionmentioning

confidence: 99%

“…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). Neural tissue-specific expression of NELL2 has been reported in developing and post-natal rats (Kim et al, 2002;Nelson et al, 2004;Oyasu et al, 2000) and humans (Watanabe et al, 1996). NELL2 mRNA is predominantly expressed in the central nervous system throughout the pre-natal stages, and its expression gradually increases during embryonic development.…”

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%

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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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Proteomic characterization of early-stage differentiation of mouse embryonic stem cells into neural cells induced byall-trans retinoic acidin vitro

et al. 2001

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Embryonic stem (ES) cells are totipotent stem cells, which can differentiate into various kinds of cell types, including neurons. They are widely used as a model system for investigating mechanisms of differentiation events during early mouse development. In this study, proteomic techniques were used to approach the protein profile associated with the early-stage differentiation of ES cells into neuronal cells induced by all-trans retinoic acid (ATRA) in vitro. In comparison of the protein profile of parent ES cells with that of ES-derived neural-committed cells, which was induced by ATRA for four days, 24 differentially displayed protein spots were selected from two-dimensional electrophoresis (2-DE) gels for further protein identification by pepide mass fingerprinting (PMF). Nine proteins were known to being involved in the process of neural differentiation and/or neural survival. Of those, alpha-3/alpha-7 tubulin and vimentin were down-regulated, while cytokeratin 8, cytokeratin 18, G1/S-special cyclin D2, follistatin-related protein, NEL protein, platelet-activating factor acetylhydrolase IB alpha-subunit, and thioredoxin peroxidase 2 were upregulated during differentiation of ES cells to neural cells. Additionally, other 12 protein (five upregulated and seven downregulated) spots associated with ES cell differentiation into neuronal cells were not matched to known proteins so far, implicating that they might be novel proteins. The results above indicated that the molecular mechanisms of differentiation of ES cells to neural cells in vitro might be similar to those of other neural systems in vitro and identified that proteomic analysis is an effective strategy to comprehensively unravel the regulatory network of differentiation.

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Cloning and Characterization of Two Novel Human cDNAs (NELL1 and NELL2) Encoding Proteins with Six EGF-like Repeats

Cited by 122 publications

References 0 publications

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

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

Proteomic characterization of early-stage differentiation of mouse embryonic stem cells into neural cells induced byall-trans retinoic acidin vitro

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