We have isolated and characterized highly proliferative stem cells from the fetal and adult mouse olfactory bulb that differentiate into the three types of neural cells, neurones, astrocytes and oligodendrocytes. The knockout mice for IGF-I has diminished the formation of neurones, astrocytes and oligodendrocytes derived from olfactory bulb stem cells and this factor promotes the differentiation of stem cells in culture to neurons and glia activating the PI3K/Akt pathway. The phosphatase PTEN, negative regulator of the PI3K/Akt pathway, diminishes the proportion of neurons and astrocytes, contributing to fine regulation of neurogenesis. Among the neuronal precursors generated locally in the olfactory bulb there are mature GABAergic and dopaminergic neurons. IGF-I promotes neuronal migration and positioning in the olfactory bulb and the exit of neuroblasts from the subventricular zone. The transcription factor Tbr-1 is expressed in the in olfactory bulb since E12.5 and its overexpression in proliferative precursors in culture increases the number of neurons and oligodendrocytes whereas diminishes GFAP+ astrocytes. This finding can be of interest in strategies of neuroregeneration. Presently, we are studying the role of autophagy in neuronal differentiation.
Méndez-Gómez HR, Vergaño-Vera E, Abad JL, Bulfone A, Moratalla R, de Pablo F, Vicario-Abejón C  The T-box brain 1 (Tbr1) transcription factor inhibits astrocyte formation in the olfactory bulb and regulates neural stem cell fate. Mol Cell Neurosci DOI:10.1016/j.mcn.2010.08.011
Hurtado-Chong A, Yusta-Boyo MJ, Vergaño-Vera E, Bulfone A, de Pablo F, Vicario-Abejón C  IGF-I promotes neuronal migration and positioning in the olfactory bulb and the exit of neuroblasts from the subventricular zone. Eur J Neurosci 30:742-755
Flora de Pablo. Células madre neurales, neurogénesis y neuroprotección. En: Células Madre y Terapia Regenerativa, F. de Pablo y M. Cascales Angosto (eds.) Monografía XXVII, Real Academia Nacional de Farmacia, 2009, pp 101-130. www.analesranf.com/index.php/mono
Coordinator: Flora de Pablo
(MD, PhD 1979, postdoctoral Fellow NIH, USA, Associate Investigator NIH and Caltech, USA).
Participants: Ana M. Robles Lobo and Patricia Vázquez.
In collaboration with Carlos Vicario-Abejón (Instituto Cajal, CSIC, Madrid).