title: Neural stem cells secrete factors facilitating brain regeneration upon constitutive Raf-Erk activation.
abstract: The intracellular Raf-Erk signaling pathway is activated during neural stem cell (NSC) proliferation, and neuronal and astrocytic differentiation. A key question is how this signal can evoke multiple and even opposing NSC behaviors. We show here, using a constitutively active Raf (ca-Raf), that Raf-Erk activation in NSCs induces neuronal differentiation in a cell-autonomous manner. By contrast, it causes NSC proliferation and the formation of astrocytes in an extrinsic autocrine/paracrine manner. Thus, treatment of NSCs with medium (CM) conditioned in ca-Raf-transduced NSCs (Raf-CM; RCM) became activated to form proliferating astrocytes resembling radial glial cells (RGCs) or adult-type NSCs. Infusion of Raf-CM into injured mouse brains caused expansion of the NSC population in the subventricular zone, followed by the formation of new neurons that migrated to the damaged site. Our study shows an example how molecular mechanisms dissecting NSC behaviors can be utilized to develop regenerative therapies in brain disorders.
authors.affiliation: Department of Biochemistry and Molecular Biology, College of Medicine, Hanyang University, Seoul, Korea.|Hanyang Biomedical Research Institute, Hanyang University, Seoul, Korea.
authors.forename: Yong-Hee
authors.initials: YH
authors.lastname: Rhee
authors.affiliation: Department of Biochemistry and Molecular Biology, College of Medicine, Hanyang University, Seoul, Korea.|Hanyang Biomedical Research Institute, Hanyang University, Seoul, Korea.
authors.forename: Sang-Hoon
authors.initials: SH
authors.lastname: Yi
authors.affiliation: Department of Anatomy, College of Medicine, Korea University, Seoul, Korea.
authors.forename: Joo Yeon
authors.initials: JY
authors.lastname: Kim
authors.affiliation: Department of Biochemistry and Molecular Biology, College of Medicine, Hanyang University, Seoul, Korea.|Hanyang Biomedical Research Institute, Hanyang University, Seoul, Korea.
authors.forename: Mi-Yoon
authors.initials: MY
authors.lastname: Chang
authors.affiliation: Department of Biochemistry and Molecular Biology, College of Medicine, Hanyang University, Seoul, Korea.|Hanyang Biomedical Research Institute, Hanyang University, Seoul, Korea.
authors.forename: A-Young
authors.initials: AY
authors.lastname: Jo
authors.affiliation: Department of Biochemistry and Molecular Biology, College of Medicine, Hanyang University, Seoul, Korea.|Hanyang Biomedical Research Institute, Hanyang University, Seoul, Korea.
authors.forename: Jinyoung
authors.initials: J
authors.lastname: Kim
authors.affiliation: Hanyang Biomedical Research Institute, Hanyang University, Seoul, Korea.|Graduate School of Biomedical Science and Engineering, Hanyang University, Seoul, Korea.|Department of Microbiology, College of Medicine, Hanyang University, Seoul, Korea.
authors.forename: Chang-Hwan
authors.initials: CH
authors.lastname: Park
authors.affiliation: Department of Biochemistry, BK21 PLUS Program for Creative Veterinary Science Research and Research Institute for Veterinary Science, College of Veterinary Medicine, Seoul National University, Seoul, South Korea.
authors.forename: Je-Yoel
authors.initials: JY
authors.lastname: Cho
authors.affiliation: ProtAnBio, Co., Seoul, South Korea.
authors.forename: Young-Jin
authors.initials: YJ
authors.lastname: Choi
authors.affiliation: Department of Anatomy, College of Medicine, Korea University, Seoul, Korea.
authors.forename: Woong
authors.initials: W
authors.lastname: Sun
authors.affiliation: Department of Biochemistry and Molecular Biology, College of Medicine, Hanyang University, Seoul, Korea.|Hanyang Biomedical Research Institute, Hanyang University, Seoul, Korea.|Graduate School of Biomedical Science and Engineering, Hanyang University, Seoul, Korea.
authors.forename: Sang-Hun
authors.initials: SH
authors.lastname: Lee
mesh_terms: D000818:Animals; D001253:Astrocytes / Q000166:cytology; D001921:Brain / Q000196:embryology / Q000502:physiology*; D002452:Cell Count; D002454:Cell Differentiation; D002478:Cells, Cultured; D017077:Culture Media, Conditioned / Q000494:pharmacology; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism*; D005904:Glial Fibrillary Acidic Protein / Q000235:genetics / Q000378:metabolism; D008297:Male; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D058953:Neural Stem Cells / Q000166:cytology / Q000378:metabolism*; D009474:Neurons / Q000166:cytology / Q000378:metabolism; D017207:Rats, Sprague-Dawley; D012038:Regeneration / Q000502:physiology*; D048490:raf Kinases / Q000378:metabolism*
chemical_list: D017077:Culture Media, Conditioned; D005904:Glial Fibrillary Acidic Protein; C528900:glial fibrillary astrocytic protein, mouse; D048490:raf Kinases; D048049:Extracellular Signal-Regulated MAP Kinases