NDLI: Oct4 is required for lineage priming in the developing inner cell mass of the mouse blastocyst.

Content Provider	World Health Organization (WHO)-Global Index Medicus
Author	Le Bin, Gloryn Chia Muñoz-Descalzo, Silvia Kurowski, Agata Leitch, Harry Lou, Xinghua Mansfield, William Etienne-Dumeau, Charles Grabole, Nils Mulas, Carla Niwa, Hitoshi Hadjantonakis, Anna-Katerina Nichols, Jennifer
Description	Country affiliation: United kingdom Author Affiliation: Le Bin GC ( Wellcome Trust - Medical Research Council Cambridge Stem Cell Institute, University of Cambridge, Tennis Court Road, Cambridge CB2 1QR, UK.)
Abstract	The transcription factor Oct4 is required in vitro for establishment and maintenance of embryonic stem cells and for reprogramming somatic cells to pluripotency. In vivo, it prevents the ectopic differentiation of early embryos into trophoblast. Here, we further explore the role of Oct4 in blastocyst formation and specification of epiblast versus primitive endoderm lineages using conditional genetic deletion. Experiments involving mouse embryos deficient for both maternal and zygotic Oct4 suggest that it is dispensable for zygote formation, early cleavage and activation of Nanog expression. Nanog protein is significantly elevated in the presumptive inner cell mass of Oct4 null embryos, suggesting an unexpected role for Oct4 in attenuating the level of Nanog, which might be significant for priming differentiation during epiblast maturation. Induced deletion of Oct4 during the morula to blastocyst transition disrupts the ability of inner cell mass cells to adopt lineage-specific identity and acquire the molecular profile characteristic of either epiblast or primitive endoderm. Sox17, a marker of primitive endoderm, is not detected following prolonged culture of such embryos, but can be rescued by provision of exogenous FGF4. Interestingly, functional primitive endoderm can be rescued in Oct4-deficient embryos in embryonic stem cell complementation assays, but only if the host embryos are at the pre-blastocyst stage. We conclude that cell fate decisions within the inner cell mass are dependent upon Oct4 and that Oct4 is not cell-autonomously required for the differentiation of primitive endoderm derivatives, as long as an appropriate developmental environment is established.
File Format	HTM / HTML
ISSN	09501991
e-ISSN	14779129
DOI	10.1242/dev.096875
Journal	Development
Issue Number	5
Volume Number	141
Language	English
Publisher	The Company of Biologists
Publisher Date	2014-03-01
Publisher Place	Great Britain (UK)
Access Restriction	Open
Subject Keyword	Discipline Developmental Discipline Biology Blastocyst Metabolism Octamer Transcription Factor-3 Animals Cytology Embryo, Mammalian Endoderm Gene Expression Regulation, Developmental Hmgb Proteins Genetics Homeodomain Proteins Mice Morula Oocytes Pregnancy Soxf Transcription Factors Zygote Research Support, N.i.h., Extramural Research Support, Non-u.s. Gov't
Content Type	Text
Resource Type	Article
Subject	Developmental Biology Molecular Biology

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