title: The microtubule destabilizing protein stathmin controls the transition from dividing neuronal precursors to postmitotic neurons during adult hippocampal neurogenesis.
abstract: The hippocampus is one of the two areas in the mammalian brain where adult neurogenesis occurs. Adult neurogenesis is well known to be involved in hippocampal physiological functions as well as pathophysiological conditions. Microtubules (MTs), providing intracellular transport, stability, and transmitting force, are indispensable for neurogenesis by facilitating cell division, migration, growth, and differentiation. Although there are several examples of MT-stabilizing proteins regulating different aspects of adult neurogenesis, relatively little is known about the function of MT-destabilizing proteins. Stathmin is such a MT-destabilizing protein largely restricted to the CNS, and in contrast to its developmental family members, stathmin is also expressed at significant levels in the adult brain, notably in areas involved in adult neurogenesis. Here, we show an important role for stathmin during adult neurogenesis in the subgranular zone of the mouse hippocampus. After carefully mapping stathmin expression in the adult dentate gyrus (DG), we investigated its role in hippocampal neurogenesis making use of stathmin knockout mice. Although hippocampus development appears normal in these animals, different aspects of adult neurogenesis are affected. First, the number of proliferating Ki-67+ cells is decreased in stathmin knockout mice, as well as the expression of the immature markers Nestin and PSA-NCAM. However, newborn cells that do survive express more frequently the adult marker NeuN and have a more mature morphology. Furthermore, our data suggest that migration in the DG might be affected. We propose a model in which stathmin controls the transition from neuronal precursors to early postmitotic neurons.
authors.affiliation: Department of Neuroscience, Erasmus Medical Centre, Rotterdam, The Netherlands; Department of Cell Biology, Faculty of Science, University of Utrecht, Utrecht, The Netherlands.
authors.forename: Karin
authors.initials: K
authors.lastname: Boekhoorn
authors.forename: Vera
authors.initials: V
authors.lastname: van Dis
authors.forename: Erika
authors.initials: E
authors.lastname: Goedknegt
authors.forename: André
authors.initials: A
authors.lastname: Sobel
authors.forename: Paul J
authors.initials: PJ
authors.lastname: Lucassen
authors.forename: Casper C
authors.initials: CC
authors.lastname: Hoogenraad
mesh_terms: D000818:Animals; D002465:Cell Movement / Q000502:physiology; D002470:Cell Survival / Q000502:physiology; D004268:DNA-Binding Proteins; D006624:Hippocampus / Q000166:cytology / Q000502:physiology*; D019394:Ki-67 Antigen / Q000378:metabolism; D008297:Male; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009419:Nerve Tissue Proteins / Q000378:metabolism; D064231:Nestin / Q000378:metabolism; D039842:Neural Cell Adhesion Molecule L1 / Q000378:metabolism; D058953:Neural Stem Cells / Q000166:cytology / Q000502:physiology*; D055495:Neurogenesis / Q000502:physiology*; D009474:Neurons / Q000166:cytology / Q000502:physiology*; D009687:Nuclear Proteins / Q000378:metabolism; D012794:Sialic Acids / Q000378:metabolism; D050777:Stathmin / Q000235:genetics / Q000378:metabolism*
chemical_list: D004268:DNA-Binding Proteins; D019394:Ki-67 Antigen; D009419:Nerve Tissue Proteins; C577485:Nes protein, mouse; D064231:Nestin; C492380:NeuN protein, mouse; D039842:Neural Cell Adhesion Molecule L1; D009687:Nuclear Proteins; D012794:Sialic Acids; D050777:Stathmin; C493994:Stmn1 protein, mouse; C103469:polysialyl neural cell adhesion molecule
keywords: adult neurogenesis; differentiation; hippocampus; microtubules; stathmin