1. Oct4 is required ~E7.5 for proliferation in the primitive streak.
- Author
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DeVeale B, Brokhman I, Mohseni P, Babak T, Yoon C, Lin A, Onishi K, Tomilin A, Pevny L, Zandstra PW, Nagy A, and van der Kooy D
- Subjects
- Animals, Cell Lineage, Cell Proliferation, Embryonic Development, Embryonic Stem Cells cytology, Gene Expression Regulation, Developmental, Mice, Neural Tube Defects etiology, Neural Tube Defects genetics, Neural Tube Defects pathology, Octamer Transcription Factor-3 antagonists & inhibitors, Octamer Transcription Factor-3 genetics, Pluripotent Stem Cells cytology, Primitive Streak growth & development, Primitive Streak metabolism, SOXB1 Transcription Factors antagonists & inhibitors, SOXB1 Transcription Factors genetics, SOXB1 Transcription Factors metabolism, Cell Differentiation genetics, Embryonic Stem Cells metabolism, Octamer Transcription Factor-3 metabolism, Pluripotent Stem Cells metabolism
- Abstract
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., Competing Interests: The authors have declared that no competing interests exist.
- Published
- 2013
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