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NELL1 and NELL2 encode cysteine-rich amino acid sequences including six epidermal growth factor-like motifs, which contain signal peptides at the N-terminals. The deduced amino acid sequences of both genes are 55% identical and their cysteine stretch structures are conserved. NELL1 is expressed in the brain and kidney, whereas NELL2 is expressed specifically in the brain. The cell lineage expressing NELLs in the nervous system was investigated in established cell lines and central nervous system tumor tissues obtained from patients by Northern blot and reverse transcriptase-polymerase chain reaction analyses. NELL1 and NELL2 were predominantly expressed in neuroblastoma cell lines and little expressed in glioblastoma cell lines. NELL1 and NELL2 were also expressed in central neurocytoma, medulloblastoma, and some astrocytic tumors. Immunohistochemical analysis revealed that NELL2 protein was localized in the cytoplasm of neurons. These results suggest that NELL2 is predominantly expressed in the neuronal cell lineage in the human nervous system. NELL1 is expressed mainly in tumors in the neuronal cell lineage.

Brain Specific Human Genes, NELL1 and NELL2, Are Predominantly Expressed in Neuroblastoma and Other Embryonal Neuroepithelial Tumors