Disease relevance of NELL2

• Additionally, the NELL1 and NELL2 mRNAs were found to be expressed abundantly in Burkitt's lymphoma Raji cells and colorectal adenocarcinoma SW480 cells, respectively [1].
• NELL1 and NELL2 were predominantly expressed in neuroblastoma cell lines and little expressed in glioblastoma cell lines [2].
• NELL1 and NELL2 were also expressed in central neurocytoma, medulloblastoma, and some astrocytic tumors [2].
• Brain specific human genes, NELL1 and NELL2, are predominantly expressed in neuroblastoma and other embryonal neuroepithelial tumors [2].
• We previously identified a secreted glycoprotein, neural epidermal growth factor-like like 2 (NELL2), in a subtraction screen designed to identify molecules regulating sensory neurogenesis and differentiation in the chick dorsal root ganglion (DRG) [3].

High impact information on NELL2

• Carcinomas express NRP1, whereas neuronal tumors and melanomas predominantly express NRP2 [4].
• For example, SEMA3F, which binds specifically to NRP2, inhibits tumor angiogenesis and metastasis [4].
• NELL2 promotes motor and sensory neuron differentiation and stimulates mitogenesis in DRG in vivo [3].
• These studies implicate dual functions for NELL2 in both the cell autonomous differentiation of neural progenitor cells while simultaneously exerting paracrine proliferative activity [3].
• Characterization of NELL2 expression during embryogenesis revealed that NELL2 was specifically expressed during the peak periods of both sensory and motor neuron differentiation, and within the neural crest was restricted to the sensory lineage [3].

Biological context of NELL2

• The cDNAs, designated NELL1 (nel-like, type 1) and NELL2 (nel-like, type 2), contained open reading frames encoding 810 and 816 amino acids, respectively [5].
• During mouse embryogenesis, expression of the NELL2 mRNA is initiated 7-11 days postcoitum, simultaneously with neural plate formation [1].
• Two closely related genes coding for NELL proteins (NELL1 and NELL2) have been cloned by the yeast two-hybrid screening of a rat brain cDNA library with the regulatory domain of protein kinase C betaI (PKCbetaI) as bait [1].
• These results suggest that NELL2 is predominantly expressed in the neuronal cell lineage in the human nervous system [2].
• Similarly during muscle development, NELL2 is specifically expressed by hypaxial muscle precursor cells in the differentiating somite and derivatives in the forelimbs and body wall, but not by epaxial muscle precursors [6].

Anatomical context of NELL2

• However, leukemic cell lines corresponding to the same early differentiation stages express abundant NELL2 mRNA [7].
• The related NELL2 gene is expressed by all nucleated peripheral blood cells examined (B, T, monocyte, and natural killer cells), but not in any of the bone marrow B lineage cells at earlier stages of development [7].
• Although the NELL1 mRNA is faintly expressed in adult neural cells, the NELL2 mRNA is expressed abundantly, particularly in the pyramidal cells of rat hippocampus, showing neuronal high plasticity [1].
• Furthermore, while NELL1 and NELL2 show distinct subcellular localization in cytoplasm, they both are partially secreted into the culture medium of COS-7 cells [1].
• In investigating NELL2 expression during embryogenesis, we demonstrate here that NELL2 is highly regulated spatially and temporally, being only transiently expressed in discrete regions of the central (CNS) and peripheral nervous systems (PNS) and in a subset of mesoderm derived structures during their peak periods of development [6].

Associations of NELL2 with chemical compounds

• We have identified a secreted glycoprotein, neural epidermal growth factor-like like 2 (NELL2), in a screen designed to isolate molecules regulating sensory neuron genesis and differentiation in the dorsal root ganglia (DRG) [6].

Other interactions of NELL2

• NELL1 and NELL2 (neural epidermal growth factor-like 1 and 2) are recently described members of the epidermal growth factor gene family that have previously been shown to be expressed almost exclusively in brain tissue [7].
• The neuronal EGF-related genes NELL1 and NELL2 are expressed in hemopoietic cells and developmentally regulated in the B lineage [7].
• This is in contrast to NELL2, which is preferentially located at distinct subcellular structures involved in the secretary process, such as endoplasmic reticulum and Golgi apparatus [8].

Analytical, diagnostic and therapeutic context of NELL2

• Western blot analysis showed that cNELL2 was not present in the medium but only in lysates, while NELL2 was detected as a glycosylated larger form in both lysates and media [8].
• In situ hybridization analysis of hyperplastic prostate specimens demonstrated that NELL2 mRNA expression is predominantly localized in basal cells of the epithelium [9].

References