Pax6 promotes neurogenesis in human neural stem cells.
During brain embryogenesis, transcription factors drive stem cells towards neuronal fate. Here we show that the transcription factor Pax6 increased in vitro generation of neurons from striatal but not cortical neural stem cells (NSCs), derived from 6 to 9 weeks old human fetuses, without affecting survival and proliferation. Overexpression of mouse Pax6 produced increased numbers of GABA+ and DARPP-32+ (characteristic of striatum) but not glutamate+ neurons (characteristic of cortex). Pax6-overexpressing cells survived and migrated to the same extent as control cells at 1 month after intrastriatal transplantation into newborn rats and generated more neuroblasts. Overexpression of mouse Pax6 in human NSCs also leads to altered levels of lineage-appropriate genes as revealed by Q-PCR. Our data suggest that Pax6 function is conserved between species since its overexpression activates similar genes in mouse and human NSCs. Also, that Pax6 overexpression in striatal NSCs increases the number of neurons but their region-specificity is maintained.
Kallur
Therése
T
Laboratory of Neural Stem Cell Biology, Section of Restorative Neurology, Stem Cell Institute, University Hospital, Lund, Sweden.
Gisler
Ramiro
R
Lindvall
Olle
O
Kokaia
Zaal
Z
D000818:Animals; D002454:Cell Differentiation / Q000502:physiology*; D049109:Cell Proliferation; D002478:Cells, Cultured; D003342:Corpus Striatum / Q000166:cytology / Q000196:embryology / Q000378:metabolism; D005136:Eye Proteins / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology*; D018398:Homeodomain Proteins / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology*; D006801:Humans; D051379:Mice; D009474:Neurons / Q000166:cytology* / Q000502:physiology*; D000071841:PAX6 Transcription Factor; D051761:Paired Box Transcription Factors / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012097:Repressor Proteins / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology*; D033581:Stem Cell Transplantation / Q000379:methods; D013234:Stem Cells / Q000166:cytology* / Q000502:physiology*
D005136:Eye Proteins; D018398:Homeodomain Proteins; D000071841:PAX6 Transcription Factor; C000605730:PAX6 protein, human; D051761:Paired Box Transcription Factors; C000605732:Pax6 protein, mouse; C000605733:Pax6 protein, rat; D012097:Repressor Proteins