title: Apcdd1 stimulates oligodendrocyte differentiation after white matter injury.
abstract: Wnt signaling plays an essential role in developmental and regenerative myelination of the CNS, therefore it is critical to understand how the factors associated with the various regulatory layers of this complex pathway contribute to these processes. Recently, Apcdd1 was identified as a negative regulator of proximal Wnt signaling, however its role in oligodendrocyte (OL) differentiation and reymelination in the CNS remain undefined. Analysis of Apcdd1 expression revealed dynamic expression during OL development, where its expression is upregulated during differentiation. Functional studies using ex vivo and in vitro OL systems revealed that Apcdd1 promotes OL differentiation, suppresses Wnt signaling, and associates with β-catenin. Application of these findings to white matter injury (WMI) models revealed that Apcdd1 similarly promotes OL differentiation after gliotoxic injury in vivo and acute hypoxia ex vivo. Examination of Apcdd1 expression in white matter lesions from neonatal WMI and adult multiple sclerosis revealed its expression in subsets of oligodendrocyte (OL) precursors. These studies describe, for the first time, the role of Apcdd1 in OLs after WMI and reveal that negative regulators of the proximal Wnt pathway can influence regenerative myelination, suggesting a new therapeutic strategy for modulating Wnt signaling and stimulating repair after WMI.
authors.affiliation: Center for Cell and Gene Therapy, Baylor College of Medicine, Houston, Texas.
authors.forename: Hyun Kyoung
authors.initials: HK
authors.lastname: Lee
authors.affiliation: Center for Cell and Gene Therapy, Baylor College of Medicine, Houston, Texas.|Program in Developmental Biology, Baylor College of Medicine, Houston, Texas.
authors.forename: Dylan
authors.initials: D
authors.lastname: Laug
authors.affiliation: Center for Cell and Gene Therapy, Baylor College of Medicine, Houston, Texas.|Integrative Molecular and Biomedical Sciences Graduate Program, Baylor College of Medicine, Houston, Texas.
authors.forename: Wenyi
authors.initials: W
authors.lastname: Zhu
authors.affiliation: Medical Scientist Training Program, Baylor College of Medicine, Houston, Texas.|Department of Neuroscience, Baylor College of Medicine, Houston, Texas.
authors.forename: Jay M
authors.initials: JM
authors.lastname: Patel
authors.affiliation: Program in Developmental Biology, Baylor College of Medicine, Houston, Texas.
authors.forename: Kevin
authors.initials: K
authors.lastname: Ung
authors.affiliation: Program in Developmental Biology, Baylor College of Medicine, Houston, Texas.|Department of Neuroscience, Baylor College of Medicine, Houston, Texas.|Department of Human and Molecular Genetics, Baylor College of Medicine, Houston, Texas.|Duncan Neurological Research Institute, Houston, Texas.
authors.forename: Benjamin R
authors.initials: BR
authors.lastname: Arenkiel
authors.affiliation: Department of Neurology, University of California, San Francisco, San Francisco, California.
authors.forename: Stephen P J
authors.initials: SP
authors.lastname: Fancy
authors.affiliation: Department of Pathology, Texas Children's Hospital, Houston, Texas.
authors.forename: Carrie
authors.initials: C
authors.lastname: Mohila
authors.affiliation: Center for Cell and Gene Therapy, Baylor College of Medicine, Houston, Texas.|Program in Developmental Biology, Baylor College of Medicine, Houston, Texas.|Integrative Molecular and Biomedical Sciences Graduate Program, Baylor College of Medicine, Houston, Texas.|Department of Neuroscience, Baylor College of Medicine, Houston, Texas.|Duncan Neurological Research Institute, Houston, Texas.
authors.forename: Benjamin
authors.initials: B
authors.lastname: Deneen
mesh_terms: D000367:Age Factors; D000818:Animals; D002454:Cell Differentiation / Q000502:physiology*; D004195:Disease Models, Animal; D018507:Gene Expression Regulation, Developmental / Q000187:drug effects / Q000502:physiology; D049452:Green Fluorescent Proteins / Q000235:genetics / Q000378:metabolism; D006801:Humans; D000860:Hypoxia / Q000150:complications; D066298:In Vitro Techniques; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics / Q000378:metabolism*; D008244:Lysophosphatidylcholines / Q000633:toxicity; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D009836:Oligodendroglia / Q000502:physiology*; D009924:Organ Culture Techniques; D013116:Spinal Cord / Q000473:pathology; D013234:Stem Cells / Q000378:metabolism / Q000502:physiology; D014912:White Muscle Disease / Q000139:chemically induced / Q000473:pathology*; D051153:Wnt Proteins / Q000378:metabolism; D060449:Wnt Signaling Pathway / Q000187:drug effects / Q000502:physiology; D051176:beta Catenin / Q000378:metabolism
chemical_list: C549624:APCDD1 protein, human; D047908:Intracellular Signaling Peptides and Proteins; D008244:Lysophosphatidylcholines; D008565:Membrane Proteins; D051153:Wnt Proteins; D051176:beta Catenin; D049452:Green Fluorescent Proteins
keywords: Apcdd1; Wnt signaling; oligodendrocyte; white matter injury