Conditional activation of Pax6 in the developing cortex of transgenic mice causes progenitor apoptosis.
During development, Pax6 is expressed in a rostrolateral-high to caudomedial-low gradient in the majority of the cortical radial glial progenitors and endows them with neurogenic properties. Using a Cre/loxP-based approach, we studied the effect of conditional activation of two Pax6 isoforms, Pax6 and Pax6-5a, on the corticogenesis of transgenic mice. We found that activation of either Pax6 or Pax6-5a inhibits progenitor proliferation in the developing cortex. Upon activation of transgenic Pax6, specific progenitor pools with distinct endogenous Pax6 expression levels at different developmental stages show defects in cell cycle progression and in the acquisition of apoptotic or neuronal cell fate. The results provide new evidence for the complex role of Pax6 in mammalian corticogenesis.
Berger
Joachim
J
Max Planck Institute for Biophysical Chemistry, D-37077 Göttingen, Germany.
Berger
Silke
S
Tuoc
Tran Cong
TC
D'Amelio
Marcello
M
Cecconi
Francesco
F
Gorski
Jessica A
JA
Jones
Kevin R
KR
Gruss
Peter
P
Stoykova
Anastassia
A
D000818:Animals; D017209:Apoptosis / Q000502:physiology*; D049109:Cell Proliferation; D002540:Cerebral Cortex / Q000196:embryology* / Q000378:metabolism; D017931:DNA Primers; D005136:Eye Proteins / Q000235:genetics / Q000378:metabolism*; D018507:Gene Expression Regulation, Developmental; D018398:Homeodomain Proteins / Q000235:genetics / Q000378:metabolism*; D007150:Immunohistochemistry; D008156:Luciferases; D051379:Mice; D008822:Mice, Transgenic; D000071841:PAX6 Transcription Factor; D051761:Paired Box Transcription Factors / Q000235:genetics / Q000378:metabolism*; D016133:Polymerase Chain Reaction; D012097:Repressor Proteins / Q000235:genetics / Q000378:metabolism*; D013234:Stem Cells / Q000166:cytology*
D017931:DNA Primers; D005136:Eye Proteins; D018398:Homeodomain Proteins; D000071841:PAX6 Transcription Factor; D051761:Paired Box Transcription Factors; C000605732:Pax6 protein, mouse; D012097:Repressor Proteins; D008156:Luciferases