Oct4 regulates the embryonic axis and coordinates exit from pluripotency and germ layer specification in the mouse embryo
| Autor: | Carla, Mulas, Gloryn, Chia, Kenneth Alan, Jones, Andrew Christopher, Hodgson, Giuliano Giuseppe, Stirparo, Jennifer, Nichols |
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| Rok vydání: | 2017 |
| Předmět: |
Male
Pluripotent Stem Cells Pluripotency Genotype Oct4 Lineage specification Mice Imaging Three-Dimensional Animals Cell Lineage Embryo Implantation RNA Messenger reproductive and urinary physiology Embryonic axis Body Patterning Epiblast SOXB1 Transcription Factors Endoderm Gastrulation Gene Expression Regulation Developmental Cell Differentiation Nanog Homeobox Protein Embryo Mammalian Stem Cells and Regeneration Phenotype embryonic structures Mutation Female Octamer Transcription Factor-3 Biomarkers Gene Deletion Germ Layers Signal Transduction |
| Zdroj: | Development (Cambridge, England) |
| ISSN: | 1477-9129 |
| Popis: | Lineage segregation in the mouse embryo is a finely controlled process dependent upon coordination of signalling pathways and transcriptional responses. Here we employ a conditional deletion system to investigate embryonic patterning and lineage specification in response to loss of Oct4. We first observe ectopic expression of Nanog in Oct4-negative postimplantation epiblast cells. The expression domains of lineage markers are subsequently disrupted. Definitive endoderm expands at the expense of mesoderm; the anterior-posterior axis is positioned more distally and an ectopic posterior-like domain appears anteriorly, suggesting a role for Oct4 in maintaining the embryonic axis. Although primitive streak forms in the presumptive proximal-posterior region, epithelial-to-mesenchymal transition is impeded by an increase of E-cadherin, leading to complete tissue disorganisation and failure to generate germ layers. In explant and in vitro differentiation assays, Oct4 mutants also show upregulation of E-cadherin and Foxa2, suggesting a cell-autonomous phenotype. We confirm requirement for Oct4 in self-renewal of postimplantation epiblast ex vivo. Our results indicate a role for Oct4 in orchestrating multiple fates and enabling expansion, correct patterning and lineage choice in the postimplantation epiblast. Highlighted Article: Ectopic expression of Nanog, expansion of the presumptive endodermal domain and trapping of cells in the primitive streak ultimately result in consistent disrupted phenotype with loss of embryonic structures. |
| Databáze: | OpenAIRE |
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