NELL2 Function in Axon Development of Hippocampal Neurons

• Published in: Molecules and cells Vol. 43; no. 6; pp. 581 - 589
• Main Authors: Kim, Han Rae, Kim, Dong Hee, An, Ji Young, Kang, Dasol, Park, Jeong Woo, Hwang, Eun Mi, Seo, Eun Jin, Jang, Il Ho, Ha, Chang Man, Lee, Byung Ju
• Format: Journal Article
• Language: English
• Published: United States Korean Society for Molecular and Cellular Biology 01.06.2020; 한국분자세포생물학회
• Subjects: Animals; Axons - metabolism; Cell Differentiation; Cell Polarity; Cells, Cultured; Hippocampus - cytology; Nerve Tissue Proteins - metabolism; Neurogenesis; Rats; RNA, Small Interfering - metabolism; Signal Transduction; 생물학; neuronal polarity; extracellular signal-regulated kinase; axon growth; hippocampal neurons; neural epidermal growth factor-like like protein 2
• ISSN: 1016-8478; 0219-1032
• DOI: 10.14348/molcells.2020.0032

Neurons have multiple dendrites and single axon. This neuronal polarity is gradually established during early processes of neuronal differentiation: generation of multiple neurites (stages 1-2); differentiation (stage 3) and maturation (stages 4-5) of an axon and dendrites. In this study, we demonstrated that the neuron-specific n-glycosylated protein NELL2 is important for neuronal polarization and axon growth using cultured rat embryonic hippocampal neurons. Endogenous NELL2 expression was gradually increased in parallel with the progression of developmental stages of hippocampal neurons, and overexpression of NELL2 stimulated neuronal polarization and axon growth. In line with these results, knockdown of NELL2 expression resulted in deterioration of neuronal development, including inhibition of neuronal development progression, decreased axon growth and increased axon branching. Inhibitor against extracellular signal-regulated kinase (ERK) dramatically inhibited NELL2-induced progression of neuronal development and axon growth. These results suggest that NELL2 is an important regulator for the morphological development for neuronal polarization and axon growth.