title: Postnatal subventricular zone of the neocortex contributes GFAP+ cells to the rostral migratory stream under the control of Sip1.
abstract: The rostral migratory stream (RMS) is composed of neuroblasts migrating from the striatal SVZ to the olfactory bulb through a meshwork of GFAP- expressing astrocytes called the glial tube. So far, the origin of the glial tube astrocytes was attributed to differentiation of Type-B stem cells of the striatal SVZ. The true identity of these cells (Type-B stem cells versus immature/mature astrocytes) is also unclear. By analyzing a neocortex-specific conditional knockout of the transcriptional repressor Sip1 (Smad-interacting protein 1), we have now identified a novel pool of progenitors located within the dorsal SVZ (dSVZ) at early postnatal stages that differentiate into GFAP+ cells of the glial tube. We show that Sip1, expressed in postmitotic cortical neurons, controls the size of this dorsal progenitor pool possibly through cell-extrinsic mechanisms. Lack of Sip1 in the neocortex causes an expansion of this population leading to an increased production of GFAP+ astrocytes/Type-B stem cells in the glial tube, and a denser intercalation of these cells with Dcx+ neuroblasts of the RMS, the consequence of which is not yet clear. Neocortex-specific Sip1 deletion also led to an expansion of Dcx+ and Tbr2+ progenitor populations in the dSVZ. We show that the dSVZ progenitors (possibly remnants of embryonic radial glia) differentiate exclusively into BLBP+ cells which migrate into the RMS and mature into GFAP+ astrocytes/Type-B stem cells at around two weeks of postnatal development. In summary, our work shows that Sip1 controls the generation of GFAP+ cells of the RMS by regulating the size of a novel progenitor pool located in the postnatal dSVZ.
authors.affiliation: Institute of Cell Biology and Neurobiology, Neurocure Cluster of Excellence, Charité - Universitätsmedizin Berlin, Campus Mitte, D-10117 Berlin, Germany. anityan@scripps.edu
authors.forename: Anjana
authors.initials: A
authors.lastname: Nityanandam
authors.forename: Srinivas
authors.initials: S
authors.lastname: Parthasarathy
authors.forename: Victor
authors.initials: V
authors.lastname: Tarabykin
mesh_terms: D000818:Animals; D002352:Carrier Proteins / Q000502:physiology*; D002450:Cell Communication; D002454:Cell Differentiation; D002465:Cell Movement; D000089662:Doublecortin Protein; D005904:Glial Fibrillary Acidic Protein; D051379:Mice; D009024:Morphogenesis; D019579:Neocortex / Q000166:cytology* / Q000502:physiology; D009419:Nerve Tissue Proteins; D016601:RNA-Binding Proteins; D013234:Stem Cells / Q000166:cytology / Q000502:physiology
chemical_list: D002352:Carrier Proteins; C000714847:Dcx protein, mouse; D000089662:Doublecortin Protein; D005904:Glial Fibrillary Acidic Protein; D009419:Nerve Tissue Proteins; D016601:RNA-Binding Proteins; C489106:Slip1 protein, mouse; C528900:glial fibrillary astrocytic protein, mouse