title: Modulated DISP3/PTCHD2 expression influences neural stem cell fate decisions.
abstract: Neural stem cells (NSCs) are defined by their dual ability to self-renew through mitotic cell division or differentiate into the varied neural cell types of the CNS. DISP3/PTCHD2 is a sterol-sensing domain-containing protein, highly expressed in neural tissues, whose expression is regulated by thyroid hormone. In the present study, we used a mouse NSC line to investigate what effect DISP3 may have on the self-renewal and/or differentiation potential of the cells. We demonstrated that NSC differentiation triggered significant reduction in DISP3 expression in the resulting astrocytes, neurons and oligodendrocytes. Moreover, when DISP3 expression was disrupted, the NSC "stemness" was suppressed, leading to a larger population of cells undergoing spontaneous neuronal differentiation. Conversely, overexpression of DISP3 resulted in increased NSC proliferation. When NSCs were cultured under differentiation conditions, we observed that the lack of DISP3 augmented the number of NSCs differentiating into each of the neural cell lineages and that neuronal morphology was altered. In contrast, DISP3 overexpression resulted in impaired cell differentiation. Taken together, our findings imply that DISP3 may help dictate the NSC cell fate to either undergo self-renewal or switch to the terminal differentiation cell program.
authors.affiliation: Institute of Molecular Genetics AS CR v.v.i., Vídeňská 1083, 142 20 Prague 4, Czech Republic.
authors.forename: Jana
authors.initials: J
authors.lastname: Konířová
authors.affiliation: Institute of Molecular Genetics AS CR v.v.i., Vídeňská 1083, 142 20 Prague 4, Czech Republic.
authors.forename: Jana
authors.initials: J
authors.lastname: Oltová
authors.affiliation: Institute of Molecular Genetics AS CR v.v.i., Vídeňská 1083, 142 20 Prague 4, Czech Republic.
authors.forename: Alicia
authors.initials: A
authors.lastname: Corlett
authors.affiliation: Institute of Molecular Genetics AS CR v.v.i., Vídeňská 1083, 142 20 Prague 4, Czech Republic.
authors.forename: Justyna
authors.initials: J
authors.lastname: Kopycińska
authors.affiliation: Institute of Molecular Genetics AS CR v.v.i., Vídeňská 1083, 142 20 Prague 4, Czech Republic.
authors.forename: Michal
authors.initials: M
authors.lastname: Kolář
authors.affiliation: Institute of Molecular Genetics AS CR v.v.i., Vídeňská 1083, 142 20 Prague 4, Czech Republic.
authors.forename: Petr
authors.initials: P
authors.lastname: Bartůněk
authors.affiliation: Institute of Molecular Genetics AS CR v.v.i., Vídeňská 1083, 142 20 Prague 4, Czech Republic.
authors.forename: Martina
authors.initials: M
authors.lastname: Zíková
mesh_terms: D001253:Astrocytes / Q000166:cytology / Q000378:metabolism; D002453:Cell Cycle / Q000235:genetics; D002454:Cell Differentiation / Q000235:genetics*; D002460:Cell Line; D049109:Cell Proliferation; D018507:Gene Expression Regulation, Developmental; D006801:Humans; D008565:Membrane Proteins / Q000235:genetics*; D058953:Neural Stem Cells / Q000166:cytology* / Q000378:metabolism*; D009474:Neurons / Q000166:cytology / Q000378:metabolism; D009836:Oligodendroglia / Q000166:cytology / Q000378:metabolism; D010641:Phenotype
chemical_list: C502279:DISP3 protein, human; D008565:Membrane Proteins