title: Non-cell-autonomous action of STAT3 in maintenance of neural precursor cells in the mouse neocortex.
abstract: The transcription factor STAT3 promotes astrocytic differentiation of neural precursor cells (NPCs) during postnatal development of the mouse neocortex, but little has been known of the possible role of STAT3 in the embryonic neocortex. We now show that STAT3 is expressed in NPCs of the mouse embryonic neocortex and that the JAK-STAT3 signaling pathway plays an essential role in the maintenance of NPCs by fibroblast growth factor 2. Conditional deletion of the STAT3 gene in NPCs reduced their capacity to form neurospheres in vitro, as well as promoted neuronal differentiation both in vitro and in vivo. Furthermore, STAT3 was found to maintain NPCs in the undifferentiated state in a non-cell-autonomous manner. STAT3-dependent expression of the Notch ligand Delta-like1 (DLL1) appears to account for the non-cell-autonomous effect of STAT3 on NPC maintenance, as knockdown of DLL1 by RNA interference or inhibition of Notch activation with a gamma-secretase inhibitor abrogated the enhancement of neurosphere formation by STAT3. Our results reveal a previously unrecognized mechanism of interaction between the JAK-STAT3 and DLL1-Notch signaling pathways, as well as a pivotal role for this interaction in maintenance of NPCs during early neocortical development.
authors.affiliation: Institute of Molecular and Cellular Biosciences, University of Tokyo, 1-1-1 Yayoi, Tokyo 113-0032, Japan.
authors.forename: Takeshi
authors.initials: T
authors.lastname: Yoshimatsu
authors.forename: Daichi
authors.initials: D
authors.lastname: Kawaguchi
authors.forename: Koji
authors.initials: K
authors.lastname: Oishi
authors.forename: Kiyoshi
authors.initials: K
authors.lastname: Takeda
authors.forename: Shizuo
authors.initials: S
authors.lastname: Akira
authors.forename: Norihisa
authors.initials: N
authors.lastname: Masuyama
authors.forename: Yukiko
authors.initials: Y
authors.lastname: Gotoh
mesh_terms: D000818:Animals; D001483:Base Sequence; D018274:Electroporation; D018507:Gene Expression Regulation, Developmental; D017403:In Situ Hybridization; D051379:Mice; D019579:Neocortex / Q000166:cytology* / Q000196:embryology*; D009474:Neurons / Q000502:physiology*; D034741:RNA, Small Interfering / Q000235:genetics; D050796:STAT3 Transcription Factor / Q000235:genetics*; D013234:Stem Cells / Q000502:physiology
chemical_list: D034741:RNA, Small Interfering; D050796:STAT3 Transcription Factor; C494087:Stat3 protein, mouse