NELL2 Function in Axon Development of Hippocampal Neurons

  • Kim, Han Rae (Department of Biological Sciences, College of Natural Sciences, University of Ulsan) ;
  • Kim, Dong Hee (Department of Biological Sciences, College of Natural Sciences, University of Ulsan) ;
  • An, Ji Young (Department of Biological Sciences, College of Natural Sciences, University of Ulsan) ;
  • Kang, Dasol (Department of Biological Sciences, College of Natural Sciences, University of Ulsan) ;
  • Park, Jeong Woo (Department of Biological Sciences, College of Natural Sciences, University of Ulsan) ;
  • Hwang, Eun Mi (Center for Functional Connectomics, Korea Institute of Science and Technology (KIST)) ;
  • Seo, Eun Jin (Department of Oral Biochemistry, Dental and Life Science Institute, Pusan National University School of Dentistry) ;
  • Jang, Il Ho (Department of Oral Biochemistry, Dental and Life Science Institute, Pusan National University School of Dentistry) ;
  • Ha, Chang Man (Research Division and Brain Research Core Facilities of Korea Brain Research Institute) ;
  • Lee, Byung Ju (Department of Biological Sciences, College of Natural Sciences, University of Ulsan)
  • Received : 2020.01.29
  • Accepted : 2020.05.24
  • Published : 2020.06.30


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.



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