title: CCN3 overexpression inhibits growth of callosal projections via upregulation of RAB25.
abstract: The cysteine-rich 61/connective tissue growth factor 3 (CCN3) is a member of the CCN family of secreted multifunctional proteins involved in a variety of cellular processes including migration, adhesion, and differentiation. Previous studies have shown that CCN3 is expressed in the developing rat central nervous system, and enhanced CCN3 expression is highly correlated with tumorigenesis. However, the expression pattern and influence of abnormal CCN3 expression during mouse cortical development remains to be elucidated. Here, we show that CCN3 expression in mice is first detectable at embryonic day 15 and increases until postnatal day 21. We overexpressed CCN3 in mouse cortical neurons using uni- and bilateral electroporation. Our in vivo overexpression experiments showed that elevated CCN3 expression inhibited the axonal outgrowth of callosal projection neurons. Moreover, we identified the small GTPase RAB25 as a downstream effector molecule of CCN3 using transcriptomic analysis with CCN3 overexpressed in cortical tissue. In vivo ectopic expression of RAB25 or the dominant-negative RAB25-T26N also revealed that the GTPase activity of RAB25 is involved in the CCN3-mediated regulation of neuronal outgrowth. Taken together, our results suggest that tight regulation of CCN3 expression is necessary for normal cortical neuronal connectivity during development, and RAB25 negatively regulates neuronal differentiation as a downstream effector of CCN3.
authors: Department of Biomedical Sciences, University of Ulsan College of Medicine, Seoul 138-736, Republic of Korea; Neuromarker Resource Bank(NRB), Seoul 138-736, Republic of Korea.
authors: Minsoo
authors: M
authors: Park
authors: Neuromarker Resource Bank(NRB), Seoul 138-736, Republic of Korea; Asan Institute for Life Sciences, Seoul 138-736, Republic of Korea.
authors: In-Jeoung
authors: IJ
authors: Baek
authors: Department of Biomedical Sciences, University of Ulsan College of Medicine, Seoul 138-736, Republic of Korea; Neuromarker Resource Bank(NRB), Seoul 138-736, Republic of Korea.
authors: Hyunduk
authors: H
authors: Kim
authors: College of Pharmacy and Research Institute of Pharmaceutical Sciences, Gyeongsang National University, Gyeongnam, Republic of Korea.
authors: Dong Kyun
authors: DK
authors: Woo
authors: Immunotherapy Research Center, Korea Research Institute of Bioscience and Biotechnology, Yuseong-gu, Daejeon, Republic of Korea. Electronic address: pyj71@kribb.re.kr.
authors: Young-Jun
authors: YJ
authors: Park
authors: Department of Biomedical Sciences, University of Ulsan College of Medicine, Seoul 138-736, Republic of Korea; Neuromarker Resource Bank(NRB), Seoul 138-736, Republic of Korea. Electronic address: sungbo@ulsan.ac.kr.
authors: Sungbo
authors: S
authors: Shim
mesh_terms: D000818:Animals; D001483:Base Sequence; D002460:Cell Line; D003337:Corpus Callosum / Q000196:embryology*; D017931:DNA Primers; D005260:Female; D051379:Mice; D008813:Mice, Inbred ICR; D055514:Nephroblastoma Overexpressed Protein / Q000378:metabolism*; D016133:Polymerase Chain Reaction; D011247:Pregnancy; D011506:Proteins / Q000378:metabolism*; D015854:Up-Regulation
chemical_list: D017931:DNA Primers; C426009:LAMTOR2 protein, mouse; D055514:Nephroblastoma Overexpressed Protein; D011506:Proteins
keywords: CCN3; Callosal projection; Cortex; Neurite outgrowth; RAB25