title: In vivo fate analysis reveals the multipotent and self-renewal features of embryonic AspM expressing cells.
abstract: Radial Glia (RG) cells constitute the major population of neural progenitors of the mouse developing brain. These cells are located in the ventricular zone (VZ) of the cerebral cortex and during neurogenesis they support the generation of cortical neurons. Later on, during brain maturation, RG cells give raise to glial cells and supply the adult mouse brain of Neural Stem Cells (NSC). Here we used a novel transgenic mouse line expressing the CreER(T2) under the control of AspM promoter to monitor the progeny of an early cohort of RG cells during neurogenesis and in the post natal brain. Long term fate mapping experiments demonstrated that AspM-expressing RG cells are multi-potent, as they can generate neurons, astrocytes and oligodendrocytes of the adult mouse brain. Furthermore, AspM descendants give also rise to proliferating progenitors in germinal niches of both developing and post natal brains. In the latter--i.e. the Sub Ventricular Zone--AspM descendants acquired several feature of neural stem cells, including the capability to generate neurospheres in vitro. We also performed the selective killing of these early progenitors by using a Nestin-GFP(flox)-TK allele. The forebrain specific loss of early AspM expressing cells caused the elimination of most of the proliferating cells of brain, a severe derangement of the ventricular zone architecture, and the impairment of the cortical lamination. We further demonstrated that AspM is expressed by proliferating cells of the adult mouse SVZ that can generate neuroblasts fated to become olfactory bulb neurons.
authors.affiliation: Department of Neuroscience, Institute of Experimental Neurology (INSPE)-San Raffaele Institute, Milan, Italy.
authors.forename: Cinzia
authors.initials: C
authors.lastname: Marinaro
authors.forename: Erica
authors.initials: E
authors.lastname: Butti
authors.forename: Andrea
authors.initials: A
authors.lastname: Bergamaschi
authors.forename: Alessandro
authors.initials: A
authors.lastname: Papale
authors.forename: Roberto
authors.initials: R
authors.lastname: Furlan
authors.forename: Giancarlo
authors.initials: G
authors.lastname: Comi
authors.forename: Gianvito
authors.initials: G
authors.lastname: Martino
authors.forename: Luca
authors.initials: L
authors.lastname: Muzio
mesh_terms: D000483:Alleles; D000818:Animals; D002148:Calmodulin-Binding Proteins; D018929:Cell Culture Techniques; D019070:Cell Lineage; D049109:Cell Proliferation; D002540:Cerebral Cortex / Q000378:metabolism / Q000473:pathology; D053595:Embryonic Stem Cells / Q000166:cytology*; D049452:Green Fluorescent Proteins / Q000378:metabolism; D051379:Mice; D008822:Mice, Transgenic; D009419:Nerve Tissue Proteins / Q000096:biosynthesis / Q000502:physiology*; D058953:Neural Stem Cells / Q000166:cytology*; D009457:Neuroglia / Q000166:cytology*; D016548:Prosencephalon / Q000473:pathology; D013997:Time Factors
chemical_list: C512460:ASPM protein, mouse; D002148:Calmodulin-Binding Proteins; D009419:Nerve Tissue Proteins; D049452:Green Fluorescent Proteins