The neurogenesis-controlling factor, Pax6, inhibits proliferation and promotes maturation in murine astrocytes.
Astrocytes serve various important functions in the CNS, but the molecular mechanisms of their generation and maturation are still enigmatic. Here, we show that Pax6, a key transcription factor that controls neurogenesis, also regulates proliferation, differentiation, and migration of astrocytes in the CNS. We first reveal that Pax6 is expressed in astrocytes during development as well as postnatally in the wild-type mouse. Astrocytes derived from Pax6 homozygous mutants (Sey/Sey) mice exhibited aberrant proliferation together with immature differentiation, both in vivo and in vitro, with higher migration potential in scratch-wound assays in vitro. Furthermore, a larger population of Sey/Sey astrocytes expresses neural stem cell markers such as nestin, Sox2, and prominin-1. These phenotypes of Pax6-deficient astrocytes putatively occur via higher Akt activity. Thus, the breakdown of Pax6 function induces the retention of neural stem-like characteristics and inhibits astrocyte maturation.
Sakurai
Katsuyasu
K
Division of Developmental Neuroscience, Center for Translational and Advanced Animal Research, Tohoku University Graduate School of Medicine, Sendai 980-8575, Japan.
Osumi
Noriko
N
D000818:Animals; D001253:Astrocytes / Q000187:drug effects / Q000502:physiology*; D001973:Bromodeoxyuridine / Q000378:metabolism; D002452:Cell Count / Q000379:methods; D002454:Cell Differentiation / Q000502:physiology*; D002465:Cell Movement / Q000235:genetics; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D002540:Cerebral Cortex / Q000166:cytology; D004622:Embryo, Mammalian; D027341:Excitatory Amino Acid Transporter 1 / Q000378:metabolism; D005136:Eye Proteins / Q000502:physiology*; D018507:Gene Expression Regulation, Developmental / Q000502:physiology*; D049452:Green Fluorescent Proteins / Q000378:metabolism; D018398:Homeodomain Proteins / Q000502:physiology*; D051379:Mice; D008813:Mice, Inbred ICR; D008817:Mice, Mutant Strains; D009154:Mutation / Q000502:physiology; D009419:Nerve Tissue Proteins / Q000378:metabolism; D051058:Oncogene Protein v-akt / Q000378:metabolism; D000071841:PAX6 Transcription Factor; D051761:Paired Box Transcription Factors / Q000172:deficiency / Q000502:physiology*; D012097:Repressor Proteins / Q000502:physiology*; D013116:Spinal Cord / Q000166:cytology / Q000196:embryology; D013234:Stem Cells; D014162:Transfection
D027341:Excitatory Amino Acid Transporter 1; D005136:Eye Proteins; D018398:Homeodomain Proteins; D009419:Nerve Tissue Proteins; D000071841:PAX6 Transcription Factor; D051761:Paired Box Transcription Factors; C000605732:Pax6 protein, mouse; D012097:Repressor Proteins; C493393:Slc1a3 protein, mouse; D049452:Green Fluorescent Proteins; D051058:Oncogene Protein v-akt; D001973:Bromodeoxyuridine