NELL2 (Neuronal Epidermal Growth Factor-like Protein 2) is a conserved secreted glycoprotein encoded by the NELL2 gene, characterized by multiple epidermal growth factor (EGF)-like repeats that support protein-protein interactions in the extracellular space. It is primarily expressed in the central nervous system throughout development into adulthood, with significant enrichment in the cortex, hippocampus, and cerebellum. Functionally, NELL2 is involved in neuronal differentiation, survival, and synaptic maturation, and supports neurite outgrowth and axonal guidance. Mechanistically, NELL2 has been reported to interact with specific guidance molecules and cell surface receptor systems, including interactions with the Roundabout receptor family (particularly ROBO3), thereby participating in regulating the guidance of crossing axons. As a secreted ligand, NELL2 can regulate downstream signaling pathways, such as the MAPK/ERK pathway and calcium-dependent processes, in an autocrine and paracrine manner, thus influencing transcriptional programs related to neural plasticity.
NELL2 adenoviral particles are recombinant adenoviral vectors engineered for efficient transient expression of NELL2 cDNA in various cell types, including post-mitotic neurons. In vitro, they facilitate gain-of-function analyses in primary neuronal cultures, human iPSC-derived neurons, glial cells, and organoid systems, allowing researchers to study its effects on neurite morphology, synaptic marker expression, electrophysiological properties, and transcriptional responses. Because NELL2 is a secreted protein, adenoviral delivery also enables paracrine and co-culture models to study ligand-receptor interactions, pathway activation, and network-level outcomes. In ex vivo and in vivo settings, NELL2 adenoviral particles support regional or cell type-specific expression for studying axonal guidance, synaptic remodeling, injury response, and circuit plasticity in developmental, neurodegenerative disease, or trauma models.
Sarcomas produce an aberrant extracellular matrix (ECM), which in turn provides informative cues for cell growth and invasion. Neural EGF-like molecule 1 (NELL1) is a secreted glycoprotein characterized by its non-neoplastic osteoinductive properties, but it is highly expressed in skeletal sarcomas. Here, researchers show that genetic deletion of NELL1 significantly reduces the invasive behavior of human osteosarcoma (OS) cell lines. NELL1 deletion results in reduced OS disease progression, suppression of metastasis, and improved survival in xenograft mouse models. Transcriptomic and phosphoproteomic analyses revealed that NELL1 deletion skews matricellular protein expression associated with diminished FAK signaling. Culturing NELL1 knockout sarcoma cells on matricellular proteins enriched in wild-type OS reverses the phenotypic and signaling changes caused by NELL1 deficiency. In sarcoma patients, high NELL1 expression correlates with decreased overall survival. These findings in mouse and human models suggest that NELL1 expression alters the sarcoma ECM to modulate cell invasive potential and prognosis. Disruption of NELL1 signaling may represent a novel therapeutic approach to shorten the time to disease progression in sarcomas.
Expression of NELL1 transcripts was observed as a conserved feature in all human OS cell lines examined. Here, researchers first performed gene deletion studies using the 143B cell line, generating six NELL1 KO clones using CRISPR/Cas9. Multiple cellular effects were observed in NELL1 KO cell clones compared to vector controls, including reduced proliferation, attachment, and invasion. Similar results were observed in analysis of a polyclonal NELL1 KO 143B cell population and were recapitulated in similar assessments in five other available OS cell lines. Overexpression studies were performed, in which adenoviral NELL1 (Ad-NELL1) delivery resulted in partial restoration of gene expression and almost complete restoration of the attachment and invasion potential of NELL1 KO 143B sarcoma cells (Figure 1K-M). These data confirm that the NELL1 gene plays a critical role in maintaining the cellular proliferation, attachment, and invasion potential of OS cells.
Figure 1. Effects of adenoviral NELL1 (Ad-NELL1) among 143B cells with or without NELL1 gene deletion. (Qin Q, et al., 2022)
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Excellent Transfection Efficiency!
The NELL2 adenoviral particles from Creative Biogene delivered exceptional transduction efficiency in our neuronal studies. The purity and titer were as promised, and the results were highly reproducible.
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