Oct4 is required ~E7.5 for proliferation in the primitive streak.
Oct4 is a widely recognized pluripotency factor as it maintains Embryonic Stem (ES) cells in a pluripotent state, and, in vivo, prevents the inner cell mass (ICM) in murine embryos from differentiating into trophectoderm. However, its function in somatic tissue after this developmental stage is not well characterized. Using a tamoxifen-inducible Cre recombinase and floxed alleles of Oct4, we investigated the effect of depleting Oct4 in mouse embryos between the pre-streak and headfold stages, ~E6.0-E8.0, when Oct4 is found in dynamic patterns throughout the embryonic compartment of the mouse egg cylinder. We found that depletion of Oct4 ~E7.5 resulted in a severe phenotype, comprised of craniorachischisis, random heart tube orientation, failed turning, defective somitogenesis and posterior truncation. Unlike in ES cells, depletion of the pluripotency factors Sox2 and Oct4 after E7.0 does not phenocopy, suggesting that ~E7.5 Oct4 is required within a network that is altered relative to the pluripotency network. Oct4 is not required in extraembryonic tissue for these processes, but is required to maintain cell viability in the embryo and normal proliferation within the primitive streak. Impaired expansion of the primitive streak occurs coincident with Oct4 depletion ∼E7.5 and precedes deficient convergent extension which contributes to several aspects of the phenotype.
Department of Molecular Genetics, University of Toronto, Toronto, Ontario, Canada.
Brian
B
DeVeale
Irina
I
Brokhman
Paria
P
Mohseni
Tomas
T
Babak
Charles
C
Yoon
Anthony
A
Lin
Kento
K
Onishi
Alexey
A
Tomilin
Larysa
L
Pevny
Peter W
PW
Zandstra
Andras
A
Nagy
Derek
D
van der Kooy
D000818:Animals; D002454:Cell Differentiation / Q000235:genetics*; D019070:Cell Lineage; D049109:Cell Proliferation; D047108:Embryonic Development; D053595:Embryonic Stem Cells / Q000166:cytology / Q000378:metabolism*; D018507:Gene Expression Regulation, Developmental; D051379:Mice; D009436:Neural Tube Defects / Q000209:etiology / Q000235:genetics / Q000473:pathology; D050814:Octamer Transcription Factor-3 / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D039904:Pluripotent Stem Cells / Q000166:cytology / Q000378:metabolism*; D054240:Primitive Streak / Q000254:growth & development / Q000378:metabolism; D055748:SOXB1 Transcription Factors / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism
D050814:Octamer Transcription Factor-3; C494174:Pou5f1 protein, mouse; D055748:SOXB1 Transcription Factors; C527783:Sox2 protein, mouse