title: Analysis of stem cell lineage progression in the neonatal subventricular zone identifies EGFR+/NG2- cells as transit-amplifying precursors.
abstract: In the adult subventricular zone (SVZ), astroglial stem cells generate transit-amplifying precursors (TAPs). Both stem cells and TAPs form clones in response to epidermal growth factor (EGF). However, in vivo, in the absence of sustained EGF receptor (EGFR) activation, TAPs divide a few times before differentiating into neuroblasts. The lack of suitable markers has hampered the analysis of stem cell lineage progression and associated functional changes in the neonatal germinal epithelium. Here we purified neuroblasts and clone-forming precursors from the neonatal SVZ using expression levels of EGFR and polysialylated neural cell adhesion molecule (PSANCAM). As in the adult SVZ, most neonatal clone-forming precursors did not express the neuroglia proteoglycan 2 (NG2) but displayed characteristics of TAPs, and only a subset exhibited antigenic characteristics of astroglial stem cells. Both precursors and neuroblasts were PSANCAM(+); however, neuroblasts also expressed doublecortin and functional voltage-dependent Ca(2+) channels. Neuroblasts and precursors had distinct outwardly rectifying K(+) current densities and passive membrane properties, particularly in precursors contacting each other, because of the contribution of gap junction coupling. Confirming the hypothesis that most are TAPs, cell tracing in brain slices revealed that within 2 days the majority of EGFR(+) cells had exited the cell cycle and differentiated into a progenitor displaying intermediate antigenic and functional properties between TAPs and neuroblasts. Thus, distinct functional and antigenic properties mark stem cell lineage progression in the neonatal SVZ.
authors.affiliation: Department of Neurobiology, Interdisciplinary Center for Neurosciences, University of Heidelberg, Heidelberg, Germany.
authors.forename: Tiziana
authors.initials: T
authors.lastname: Cesetti
authors.forename: Kirsten
authors.initials: K
authors.lastname: Obernier
authors.forename: C Peter
authors.initials: CP
authors.lastname: Bengtson
authors.forename: Tatiana
authors.initials: T
authors.lastname: Fila
authors.forename: Claudia
authors.initials: C
authors.lastname: Mandl
authors.forename: Gabriele
authors.initials: G
authors.lastname: Hölzl-Wenig
authors.forename: Kerstin
authors.initials: K
authors.lastname: Wörner
authors.forename: Volker
authors.initials: V
authors.lastname: Eckstein
authors.forename: Francesca
authors.initials: F
authors.lastname: Ciccolini
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D000941:Antigens / Q000378:metabolism; D001921:Brain / Q000166:cytology* / Q000378:metabolism; D002454:Cell Differentiation; D019070:Cell Lineage; D066246:ErbB Receptors / Q000378:metabolism; D005434:Flow Cytometry; D007150:Immunohistochemistry; D051379:Mice; D055495:Neurogenesis / Q000502:physiology*; D009474:Neurons / Q000166:cytology* / Q000378:metabolism; D018408:Patch-Clamp Techniques; D011509:Proteoglycans / Q000378:metabolism; D013234:Stem Cells / Q000166:cytology*; D000099216:Chondroitin Sulfate Proteoglycan 4
chemical_list: D000941:Antigens; D066246:ErbB Receptors; D011509:Proteoglycans; D000099216:Chondroitin Sulfate Proteoglycan 4