Glial cells generate neurons: the role of the transcription factor Pax6.
Radial glial cells, ubiquitous throughout the developing CNS, guide radially migrating neurons and are the precursors of astrocytes. Recent evidence indicates that radial glial cells also generate neurons in the developing cerebral cortex. Here we investigated the role of the transcription factor Pax6 expressed in cortical radial glia. We showed that radial glial cells isolated from the cortex of Pax6 mutant mice have a reduced neurogenic potential, whereas the neurogenic potential of non-radial glial precursors is not affected. Consistent with defects in only one neurogenic lineage, the number of neurons in the Pax6 mutant cortex in vivo is reduced by half. Conversely, retrovirally mediated Pax6 expression instructs neurogenesis even in astrocytes from postnatal cortex in vitro. These results demonstrated an important role of Pax6 as intrinsic fate determinant of the neurogenic potential of glial cells.
Heins
Nico
N
Max-Planck Institute of Neurobiology, Am Klopferspitz 18a, 82152, Planegg-Martinsreid, Munich, Germany.
Malatesta
Paolo
P
Cecconi
Francesco
F
Nakafuku
Masato
M
Tucker
Kerry Lee
KL
Hack
Michael A
MA
Chapouton
Prisca
P
Barde
Yves-Alain
YA
Götz
Magdalena
M
D000818:Animals; D019070:Cell Lineage; D002465:Cell Movement / Q000502:physiology*; D002469:Cell Separation; D002478:Cells, Cultured; D002540:Cerebral Cortex / Q000166:cytology / Q000196:embryology / Q000254:growth & development* / Q000502:physiology; D005136:Eye Proteins; D005434:Flow Cytometry; D049452:Green Fluorescent Proteins; D018398:Homeodomain Proteins / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D007202:Indicators and Reagents / Q000378:metabolism; D008164:Luminescent Proteins / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D009457:Neuroglia / Q000502:physiology*; D009474:Neurons / Q000502:physiology*; D000071841:PAX6 Transcription Factor; D051761:Paired Box Transcription Factors; D051381:Rats; D012097:Repressor Proteins; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism; D019076:Transgenes / Q000235:genetics
D005136:Eye Proteins; D018398:Homeodomain Proteins; D007202:Indicators and Reagents; D008164:Luminescent 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; D014157:Transcription Factors; D049452:Green Fluorescent Proteins