A novel and critical role for Oct4 as a regulator of the maternal-embryonic transition.
BACKGROUND
Compared to the emerging embryonic stem cell (ESC) gene network, little is known about the dynamic gene network that directs reprogramming in the early embryo. We hypothesized that Oct4, an ESC pluripotency regulator that is also highly expressed at the 1- to 2-cell stages in embryos, may be a critical regulator of the earliest gene network in the embryo.


RESULTS
Using antisense morpholino oligonucleotide (MO)-mediated gene knockdown, we show that Oct4 is required for development prior to the blastocyst stage. Specifically, Oct4 has a novel and critical role in regulating genes that encode transcriptional and post-transcriptional regulators as early as the 2-cell stage. Our data suggest that the key function of Oct4 may be to switch the developmental program from one that is predominantly regulated by post-transcriptional control to one that depends on the transcriptional network. Further, we propose to rank candidate genes quantitatively based on the inter-embryo variation in their differential expression in response to Oct4 knockdown. Of over 30 genes analyzed according to this proposed paradigm, Rest and Mta2, both of which have established pluripotency functions in ESCs, were found to be the most tightly regulated by Oct4 at the 2-cell stage.


CONCLUSIONS
We show that the Oct4-regulated gene set at the 1- to 2-cell stages of early embryo development is large and distinct from its established network in ESCs. Further, our experimental approach can be applied to dissect the gene regulatory network of Oct4 and other pluripotency regulators to deconstruct the dynamic developmental program in the early embryo.
Foygel
Kira
K
Department of Obstetrics and Gynecology, Stanford University School of Medicine, Stanford, California, USA.
Choi
Bokyung
B
Jun
Sunny
S
Leong
Denise E
DE
Lee
Alan
A
Wong
Connie C
CC
Zuo
Elizabeth
E
Eckart
Michael
M
Reijo Pera
Renee A
RA
Wong
Wing H
WH
Yao
Mylene W M
MW
D000818:Animals; D001755:Blastocyst; D047108:Embryonic Development / Q000235:genetics*; D053595:Embryonic Stem Cells; D005260:Female; D020869:Gene Expression Profiling; D018507:Gene Expression Regulation, Developmental; D055785:Gene Knockdown Techniques; D053263:Gene Regulatory Networks / Q000502:physiology*; D006801:Humans; D051379:Mice; D009035:Mothers; D050814:Octamer Transcription Factor-3 / Q000235:genetics* / Q000378:metabolism; D011247:Pregnancy; D012333:RNA, Messenger / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction
D050814:Octamer Transcription Factor-3; C494174:Pou5f1 protein, mouse; D012333:RNA, Messenger