title: An increase in MECP2 dosage impairs neural tube formation.
abstract: Epigenetic mechanisms are fundamental for shaping the activity of the central nervous system (CNS). Methyl-CpG binding protein 2 (MECP2) acts as a bridge between methylated DNA and transcriptional effectors responsible for differentiation programs in neurons. The importance of MECP2 dosage in CNS is evident in Rett Syndrome and MECP2 duplication syndrome, which are neurodevelopmental diseases caused by loss-of-function mutations or duplication of the MECP2 gene, respectively. Although many studies have been performed on Rett syndrome models, little is known about the effects of an increase in MECP2 dosage. Herein, we demonstrate that MECP2 overexpression affects neural tube formation, leading to a decrease in neuroblast proliferation in the neural tube ventricular zone. Furthermore, an increase in MECP2 dose provokes premature differentiation of neural precursors accompanied by greater cell death, resulting in a loss of neuronal populations. Overall, our data indicate that correct MECP2 expression levels are required for proper nervous system development.
authors.affiliation: Cancer Epigenetics and Biology Program (PEBC), Bellvitge Biomedical Research Institute (IDIBELL), 08908L'Hospitalet, Barcelona, Catalonia, Spain.
authors.forename: Paolo
authors.initials: P
authors.lastname: Petazzi
authors.affiliation: Department of Molecular Genomics, Instituto de Biología Molecular de Barcelona, Consejo Superior de Investigaciones Científicas, Barcelona, Catalonia, Spain.
authors.forename: Naiara
authors.initials: N
authors.lastname: Akizu
authors.affiliation: Department of Molecular Genomics, Instituto de Biología Molecular de Barcelona, Consejo Superior de Investigaciones Científicas, Barcelona, Catalonia, Spain.
authors.forename: Alejandra
authors.initials: A
authors.lastname: García
authors.affiliation: Department of Molecular Genomics, Instituto de Biología Molecular de Barcelona, Consejo Superior de Investigaciones Científicas, Barcelona, Catalonia, Spain.
authors.forename: Conchi
authors.initials: C
authors.lastname: Estarás
authors.affiliation: Cancer Epigenetics and Biology Program (PEBC), Bellvitge Biomedical Research Institute (IDIBELL), 08908L'Hospitalet, Barcelona, Catalonia, Spain.
authors.forename: Alexia
authors.initials: A
authors.lastname: Martínez de Paz
authors.affiliation: Cancer Epigenetics and Biology Program (PEBC), Bellvitge Biomedical Research Institute (IDIBELL), 08908L'Hospitalet, Barcelona, Catalonia, Spain.
authors.forename: Manuel
authors.initials: M
authors.lastname: Rodríguez-Paredes
authors.affiliation: Department of Molecular Genomics, Instituto de Biología Molecular de Barcelona, Consejo Superior de Investigaciones Científicas, Barcelona, Catalonia, Spain.
authors.forename: Marian A
authors.initials: MA
authors.lastname: Martínez-Balbás
authors.affiliation: Cancer Epigenetics and Biology Program (PEBC), Bellvitge Biomedical Research Institute (IDIBELL), 08908L'Hospitalet, Barcelona, Catalonia, Spain. Electronic address: dhuertas@idibell.cat.
authors.forename: Dori
authors.initials: D
authors.lastname: Huertas
authors.affiliation: Cancer Epigenetics and Biology Program (PEBC), Bellvitge Biomedical Research Institute (IDIBELL), 08908L'Hospitalet, Barcelona, Catalonia, Spain; Department of Physiological Sciences II, School of Medicine, University of Barcelona, Barcelona, Catalonia, Spain; Institució Catalana de Recerca i Estudis Avançats (ICREA), Barcelona, Catalonia, Spain. Electronic address: mesteller@idibell.cat.
authors.forename: Manel
authors.initials: M
authors.lastname: Esteller
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D017209:Apoptosis; D002645:Chickens; D018628:Gene Dosage; D006801:Humans; D051783:Methyl-CpG-Binding Protein 2 / Q000235:genetics* / Q000378:metabolism; D008969:Molecular Sequence Data; D054259:Neural Tube / Q000254:growth & development* / Q000378:metabolism*; D013116:Spinal Cord / Q000254:growth & development / Q000378:metabolism
chemical_list: C497392:MECP2 protein, human; D051783:Methyl-CpG-Binding Protein 2
keywords: Chicken neurogenesis; MECP2; Neuroblast proliferation; Rett syndrome