title: PINK1 expression increases during brain development and stem cell differentiation, and affects the development of GFAP-positive astrocytes.
abstract: BACKGROUND
  Mutation of PTEN-induced putative kinase 1 (PINK1) causes autosomal recessive early-onset Parkinson's disease (PD). Despite of its ubiquitous expression in brain, its roles in non-neuronal cells such as neural stem cells (NSCs) and astrocytes were poorly unknown.
  
  
  RESULTS
  We show that PINK1 expression increases from embryonic day 12 to postnatal day 1 in mice, which represents the main period of brain development. PINK1 expression also increases during neural stem cell (NSC) differentiation. Interestingly, expression of GFAP (a marker of astrocytes) was lower in PINK1 knockout (KO) mouse brain lysates compared to wild-type (WT) lysates at postnatal days 1-8, whereas there was little difference in the expression of markers for other brain cell types (e.g., neurons and oligodendrocytes). Further experiments showed that PINK1-KO NSCs were defective in their differentiation to astrocytes, producing fewer GFAP-positive cells compared to WT NSCs. However, the KO and WT NSCs did not differ in their self-renewal capabilities or ability to differentiate to neurons and oligodendrocytes. Interestingly, during differentiation of KO NSCs there were no defects in mitochondrial function, and there were not changes in signaling molecules such as SMAD1/5/8, STAT3, and HES1 involved in differentiation of NSCs into astrocytes. In brain sections, GFAP-positive astrocytes were more sparsely distributed in the corpus callosum and substantia nigra of KO animals compared with WT.
  
  
  CONCLUSIONS
  Our study suggests that PINK1 deficiency causes defects in GFAP-positive astrogliogenesis during brain development and NSC differentiation, which may be a factor to increase risk for PD.
authors.affiliation: Neuroscience Graduate Program Department of Biomedical Sciences, Ajou University School of Medicine, Suwon, Korea. cnscis@gmail.com.|Chronic Inflammatory Disease Research Center, Ajou University School of Medicine, Suwon, Korea. cnscis@gmail.com.
authors.forename: Insup
authors.initials: I
authors.lastname: Choi
authors.affiliation: Neuroscience Graduate Program Department of Biomedical Sciences, Ajou University School of Medicine, Suwon, Korea. djchoi81@ajou.ac.kr.
authors.forename: Dong-Joo
authors.initials: DJ
authors.lastname: Choi
authors.affiliation: Department of Pharmacology, Ajou University School of Medicine san-5, Woncheon-dong, Youngtong-gu, Suwon, Kyunggi-do, 442-721, Korea. yanghaijie168@gmail.com.
authors.forename: Haijie
authors.initials: H
authors.lastname: Yang
authors.affiliation: Chronic Inflammatory Disease Research Center, Ajou University School of Medicine, Suwon, Korea. joohongwoo@daum.net.
authors.forename: Joo Hong
authors.initials: JH
authors.lastname: Woo
authors.affiliation: Department of Biochemistry and Molecular Biology, College of Medicine, Hanyang University, Seoul, Korea. mychang@hanyang.ac.kr.
authors.forename: Mi-Yoon
authors.initials: MY
authors.lastname: Chang
authors.affiliation: Department of Anatomy and Division of Brain Korea 21 Plus Biomedical Science, Korea University College of Medicine, Seoul, 136-705, Korea. foxpporu@naver.com.
authors.forename: Joo Yeon
authors.initials: JY
authors.lastname: Kim
authors.affiliation: Department of Anatomy and Division of Brain Korea 21 Plus Biomedical Science, Korea University College of Medicine, Seoul, 136-705, Korea. woongsun@korea.ac.kr.
authors.forename: Woong
authors.initials: W
authors.lastname: Sun
authors.affiliation: Neuroscience Graduate Program Department of Biomedical Sciences, Ajou University School of Medicine, Suwon, Korea. sangmyun@ajou.ac.kr.|Chronic Inflammatory Disease Research Center, Ajou University School of Medicine, Suwon, Korea. sangmyun@ajou.ac.kr.|Department of Pharmacology, Ajou University School of Medicine san-5, Woncheon-dong, Youngtong-gu, Suwon, Kyunggi-do, 442-721, Korea. sangmyun@ajou.ac.kr.
authors.forename: Sang-Myun
authors.initials: SM
authors.lastname: Park
authors.affiliation: Neuroscience Graduate Program Department of Biomedical Sciences, Ajou University School of Medicine, Suwon, Korea. jouilo@ajou.ac.kr.|Chronic Inflammatory Disease Research Center, Ajou University School of Medicine, Suwon, Korea. jouilo@ajou.ac.kr.|Department of Pharmacology, Ajou University School of Medicine san-5, Woncheon-dong, Youngtong-gu, Suwon, Kyunggi-do, 442-721, Korea. jouilo@ajou.ac.kr.
authors.forename: Ilo
authors.initials: I
authors.lastname: Jou
authors.affiliation: Department of Biochemistry and Molecular Biology, College of Medicine, Hanyang University, Seoul, Korea. leesh@hanyang.ac.kr.
authors.forename: Sang-Hun
authors.initials: SH
authors.lastname: Lee
authors.affiliation: Department of Biochemistry and Molecular Biology, College of Medicine, Hanyang University, Seoul, Korea. leesh@hanyang.ac.kr.
authors.forename: Sang Hoon
authors.initials: SH
authors.lastname: Lee
authors.affiliation: Neuroscience Graduate Program Department of Biomedical Sciences, Ajou University School of Medicine, Suwon, Korea. ehjoe@ajou.ac.kr.|Chronic Inflammatory Disease Research Center, Ajou University School of Medicine, Suwon, Korea. ehjoe@ajou.ac.kr.|Department of Pharmacology, Ajou University School of Medicine san-5, Woncheon-dong, Youngtong-gu, Suwon, Kyunggi-do, 442-721, Korea. ehjoe@ajou.ac.kr.|Department of Brain Science, Ajou University School of Medicine, Suwon, Korea. ehjoe@ajou.ac.kr.|Brain Disease Research Center, Ajou University School of Medicine, Suwon, Korea. ehjoe@ajou.ac.kr.
authors.forename: Eun-Hye
authors.initials: EH
authors.lastname: Joe
mesh_terms: D000818:Animals; D001253:Astrocytes / Q000166:cytology* / Q000378:metabolism; D001921:Brain / Q000166:cytology / Q000196:embryology* / Q000378:metabolism*; D002454:Cell Differentiation; D049109:Cell Proliferation; D000066673:Cell Self Renewal / Q000235:genetics; D002552:Cerebral Ventricles / Q000378:metabolism; D018507:Gene Expression Regulation, Developmental; D005904:Glial Fibrillary Acidic Protein / Q000235:genetics / Q000378:metabolism*; D018345:Mice, Knockout; D008928:Mitochondria / Q000378:metabolism; D058953:Neural Stem Cells / Q000166:cytology* / Q000378:metabolism; D055495:Neurogenesis; D011494:Protein Kinases / Q000172:deficiency / Q000378:metabolism*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction / Q000235:genetics; D013378:Substantia Nigra / Q000378:metabolism; D000099202:PTEN-Induced Putative Kinase
chemical_list: D005904:Glial Fibrillary Acidic Protein; D011494:Protein Kinases; D012333:RNA, Messenger; D000099202:PTEN-Induced Putative Kinase; C528900:glial fibrillary astrocytic protein, mouse