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Published Online: 12 August 2014

Pax6 Is Essential for the Maintenance and Multi-Lineage Differentiation of Neural Stem Cells, and for Neuronal Incorporation into the Adult Olfactory Bulb

Publication: Stem Cells and Development
Volume 23, Issue Number 23

Abstract

The paired type homeobox 6 (Pax6) transcription factor (TF) regulates multiple aspects of neural stem cell (NSC) and neuron development in the embryonic central nervous system. However, less is known about the role of Pax6 in the maintenance and differentiation of adult NSCs and in adult neurogenesis. Using the +/SeyDey mouse, we have analyzed how Pax6 heterozygosis influences the self-renewal and proliferation of adult olfactory bulb stem cells (aOBSCs). In addition, we assessed its influence on neural differentiation, neuronal incorporation, and cell death in the adult OB, both in vivo and in vitro. Our results indicate that the Pax6 mutation alters Nestin+-cell proliferation in vivo, as well as self-renewal, proliferation, and survival of aOBSCs in vitro although a subpopulation of +/SeyDey progenitors is able to expand partially similar to wild-type progenitors. This mutation also impairs aOBSC differentiation into neurons and oligodendrocytes, whereas it increases cell death while preserving astrocyte survival and differentiation. Furthermore, Pax6 heterozygosis causes a reduction in the variety of neurochemical interneuron subtypes generated from aOBSCs in vitro and in the incorporation of newly generated neurons into the OB in vivo. Our findings support an important role of Pax6 in the maintenance of aOBSCs by regulating cell death, self-renewal, and cell fate, as well as in neuronal incorporation into the adult OB. They also suggest that deregulation of the cell cycle machinery and TF expression in aOBSCs which are deficient in Pax6 may be at the origin of the phenotypes observed in this adult NSC population.

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cover image Stem Cells and Development
Stem Cells and Development
Volume 23Issue Number 23December 1, 2014
Pages: 2813 - 2830
PubMed: 25117830

History

Published in print: December 1, 2014
Published ahead of print: 17 September 2014
Published online: 12 August 2014
Accepted: 12 August 2014
Received: 28 January 2014

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Gloria G. Curto
Instituto de Neurociencias de Castilla y León (INCyL), Universidad de Salamanca, Salamanca, Spain.
Vanesa Nieto-Estévez
Instituto Cajal, Consejo Superior de Investigaciones Científicas (CSIC), Madrid, Spain.
Centro de Investigación Biomédica en Red Sobre Enfermedades Neurodegenerativas (CIBERNED), Madrid, Spain.
Anahí Hurtado-Chong
Instituto Cajal, Consejo Superior de Investigaciones Científicas (CSIC), Madrid, Spain.
Jorge Valero
Instituto de Neurociencias de Castilla y León (INCyL), Universidad de Salamanca, Salamanca, Spain.
Center for Neuroscience and Cell Biology (CNC), University of Coimbra, Coimbra, Portugal.
Carmela Gómez
Instituto de Neurociencias de Castilla y León (INCyL), Universidad de Salamanca, Salamanca, Spain.
José R. Alonso*
Instituto de Neurociencias de Castilla y León (INCyL), Universidad de Salamanca, Salamanca, Spain.
Centro de Alta Investigación, Universidad de Tarapacá, Tarapacá, Chile.
Eduardo Weruaga*
Instituto de Neurociencias de Castilla y León (INCyL), Universidad de Salamanca, Salamanca, Spain.
Carlos Vicario-Abejón*
Instituto Cajal, Consejo Superior de Investigaciones Científicas (CSIC), Madrid, Spain.
Centro de Investigación Biomédica en Red Sobre Enfermedades Neurodegenerativas (CIBERNED), Madrid, Spain.

Notes

*
These authors contributed equally to this work.
Address correspondence to:Dr. Carlos Vicario-AbejónInstituto CajalConsejo Superior de Investigaciones Científicas (CSIC)Avenida Doctor Arce 37Madrid E-28002Spain
E-mail: [email protected]

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The authors have no competing financial interests to declare.

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