title: Knockdown of tissue nonspecific alkaline phosphatase impairs neural stem cell proliferation and differentiation.
abstract: In the adult mammalian brain the subependymal layer of the lateral ventricles houses neural stem cells giving rise to young neurons migrating towards the olfactory bulb. The molecular cues controlling essential functions within the neurogenesis pathway such as proliferation, short and long distance migration, differentiation and functional integration are poorly understood. Neural progenitors in situ express the tissue nonspecific form of alkaline phosphatase (TNAP), a cell surface-located nonspecific phosphomonoesterase capable of hydrolyzing extracellular nucleotides. To gain insight into the functional role of TNAP in cultured multipotent neural stem cells we applied a knockdown protocol using RNA interference with shRNA and retroviral infection. We show that TNAP knockdown reduces cell proliferation and differentiation into neurons or oligodendrocytes. This effect is abrogated by addition of alkaline phosphatase to the culture medium. Our results suggest that TNAP is essential for NSC proliferation and differentiation in vitro and possibly also in vivo.
authors.affiliation: Institute of Cell Biology and Neuroscience, Biocenter, J.W. Goethe-University, Max-von-Laue-Str. 9, 60438 Frankfurt, Germany.
authors.forename: Vanessa
authors.initials: V
authors.lastname: Kermer
authors.forename: Mathias
authors.initials: M
authors.lastname: Ritter
authors.forename: Boris
authors.initials: B
authors.lastname: Albuquerque
authors.forename: Christoph
authors.initials: C
authors.lastname: Leib
authors.forename: Matthias
authors.initials: M
authors.lastname: Stanke
authors.forename: Herbert
authors.initials: H
authors.lastname: Zimmermann
mesh_terms: D000469:Alkaline Phosphatase / Q000235:genetics* / Q000502:physiology; D000818:Animals; D015153:Blotting, Western; D002448:Cell Adhesion / Q000502:physiology; D002454:Cell Differentiation / Q000235:genetics* / Q000502:physiology*; D049109:Cell Proliferation; D002478:Cells, Cultured; D007150:Immunohistochemistry; D051379:Mice; D008822:Mice, Transgenic; D039902:Multipotent Stem Cells / Q000502:physiology; D058953:Neural Stem Cells / Q000201:enzymology* / Q000502:physiology*; D009474:Neurons / Q000502:physiology; D009836:Oligodendroglia / Q000502:physiology; D034622:RNA Interference; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics; D034741:RNA, Small Interfering / Q000096:biosynthesis / Q000235:genetics
chemical_list: D012333:RNA, Messenger; D034741:RNA, Small Interfering; C510878:ALPL protein, mouse; D000469:Alkaline Phosphatase