forcing neural progenitor cells to cycle

forcing neural progenitor cells to cycle - 13 February 2008...

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13 February 2008 Forcing neural progenitor cells to cycle is insufficient to alter cell-fate decision and timing of neuronal differentiation in the spinal cord Neural Development 2008, 3 :4 www.neuraldevelopment.com NEURAL DEVELOPMENT Valérie Lobjois et al . http://www.neuraldevelopment.com/content/3/1/4
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Bio Med Central Page 1 of 15 (page number not for citation purposes) Neural Development Open Access Research article Forcing neural progenitor cells to cycle is insufficient to alter cell-fate decision and timing of neuronal differentiation in the spinal cord Valérie Lobjois †1,2 , Sophie Bel-Vialar †1 , Françoise Trousse 1,3 and Fabienne Pituello* 1 Address: 1 Centre de Biologie du Développement, UMR5547, Institut d'Exploration Fonctionnelle des Génomes IFR109, Université Toulouse III et Centre National de la Recherche Scientifique, 31062 Toulouse, France, 2 Laboratoire de Biologie Cellulaire et Moléculaire du Contrôle de la Prolifération, UMR5088, Institut d'Exploration Fonctionnelle des Génomes IFR109, Université Toulouse III et Centre National de la Recherche Scientifique, 31062 Toulouse, France and 3 Univ Montpellier 2, Montpellier, 34095 France; Inserm, U710, Montpellier, 34095 France; EPHE, Paris, 75007 France Email: Valérie Lobjois - lobjois@cict.fr; Sophie Bel-Vialar - belviala@cict.fr; Françoise Trousse - Francoise.Trousse@univ-montp2.fr; Fabienne Pituello* - pituello@cict.fr * Corresponding author †Equal contributors Abstract Background: During the development of the nervous system, neural progenitor cells can either stay in the pool of proliferating undifferentiated cells or exit the cell cycle and differentiate. Two main factors will determine the fate of a neural progenitor cell: its position within the neuroepithelium and the time at which the cell initiates differentiation. In this paper we investigated the importance of the timing of cell cycle exit on cell-fate decision by forcing neural progenitors to cycle and studying the consequences on specification and differentiation programs. Results: As a model, we chose the spinal progenitors of motor neurons (pMNs), which switch cell-fate from motor neurons to oligodendrocytes with time. To keep pMNs in the cell cycle, we forced the expression of G1-phase regulators, the D-type cyclins. We observed that keeping neural progenitor cells cycling is not sufficient to retain them in the progenitor domain (ventricular zone); transgenic cells instead migrate to the differentiating field (mantle zone) regardless of cell cycle exit. Cycling cells located in the mantle zone do not retain markers of neural progenitor cells such as Sox2 or Olig2 but upregulate transcription factors involved in motor neuron specification, including MNR2 and Islet1/2. These cycling cells also progress through neuronal differentiation to axonal extension. We also observed mitotic cells displaying all the features of differentiating motor neurons, including axonal projection via the ventral root.
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forcing neural progenitor cells to cycle - 13 February 2008...

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