title: CHCHD2 is down-regulated in neuronal cells differentiated from iPS cells derived from patients with lissencephaly.
abstract: The human cerebral cortex is peculiar for a six-layered cellular-sheet structure with convolution, which is a consequence of neuronal migration. Dysfunctions of the pathways contributing to this mechanism typically lead to lissencephaly manifesting smooth brain surfaces. To investigate the unknown mechanism underlying neuronal migration disorders, we generated induced pluripotent stem (iPS) cells from two patients with lissencephaly. Whole gene expression study for iPS cells derived from a patient with a LIS1 deletion showed reduced expression of the coiled-coil-helix-coiled-coil-helix domain containing 2 gene (CHCHD2), which was also confirmed in iPS cells derived from a patient with a TUBA1A mutation. CHCHD2 expression was detected in neuronal cells differentiated from normal iPS cells in a time-dependent manner, as well as in the brain of a fetus at 26-28 week gestational age, suggesting development-dependent expression. Migrating neuronal cells showed CHCHD2 expression, suggesting its functional relevance to neuronal migration.
authors.affiliation: Precursory Research for Embryonic Science and Technology (PRESTO), Japan Science and Technology Agency (JST), Kawaguchi, Japan; Tokyo Women's Medical University Institute for Integrated Medical Sciences (TIIMS), Tokyo, Japan.
authors.forename: Keiko
authors.initials: K
authors.lastname: Shimojima
authors.affiliation: Department of Pediatrics, Juntendo University, Tokyo, Japan; Department of Pediatrics, Aichi Medical University, Nagakute, Japan.
authors.forename: Akihisa
authors.initials: A
authors.lastname: Okumura
authors.affiliation: Department of Brain Development and Neural Regeneration, Tokyo Metropolitan Institute of Medical Science, Tokyo, Japan.
authors.forename: Masaharu
authors.initials: M
authors.lastname: Hayashi
authors.affiliation: Center for iPS Cell Research and Application (CiRA), Kyoto University, Kyoto, Japan; Core Research for Evolutional Science and Technology (CREST), Japan Science and Technology Agency (JST), Saitama, Japan.
authors.forename: Takayuki
authors.initials: T
authors.lastname: Kondo
authors.affiliation: Center for iPS Cell Research and Application (CiRA), Kyoto University, Kyoto, Japan; Core Research for Evolutional Science and Technology (CREST), Japan Science and Technology Agency (JST), Saitama, Japan.
authors.forename: Haruhisa
authors.initials: H
authors.lastname: Inoue
authors.affiliation: Tokyo Women's Medical University Institute for Integrated Medical Sciences (TIIMS), Tokyo, Japan. Electronic address: yamamoto.toshiyuki@twmu.ac.jp.
authors.forename: Toshiyuki
authors.initials: T
authors.lastname: Yamamoto
mesh_terms: D043203:1-Alkyl-2-acetylglycerophosphocholine Esterase / Q000235:genetics; D001921:Brain / Q000196:embryology / Q000378:metabolism; D002454:Cell Differentiation; D004268:DNA-Binding Proteins; D015536:Down-Regulation; D005260:Female; D017353:Gene Deletion; D006801:Humans; D057026:Induced Pluripotent Stem Cells / Q000378:metabolism* / Q000473:pathology; D007223:Infant; D054082:Lissencephaly / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D008297:Male; D008869:Microtubule-Associated Proteins / Q000235:genetics; D024101:Mitochondrial Proteins / Q000235:genetics* / Q000378:metabolism*; D020125:Mutation, Missense; D009474:Neurons / Q000378:metabolism* / Q000473:pathology; D014157:Transcription Factors / Q000235:genetics* / Q000378:metabolism*; D014404:Tubulin / Q000235:genetics
chemical_list: C580880:CHCHD2 protein, human; D004268:DNA-Binding Proteins; D008869:Microtubule-Associated Proteins; D024101:Mitochondrial Proteins; C533522:TUBA1A protein, human; D014157:Transcription Factors; D014404:Tubulin; D043203:1-Alkyl-2-acetylglycerophosphocholine Esterase; C084102:PAFAH1B1 protein, human
keywords: Coiled-coil-helix-coiled-coil-helix domain containing 2 (CHCHD2); Induced pluripotent stem (iPS) cell; Neuronal migration disorder; PAFAH1B1 (LIS1); TUBA1A