| First Author | Mulas C | Year | 2018 |
| Journal | Development | Volume | 145 |
| Issue | 12 | PubMed ID | 29915126 |
| Mgi Jnum | J:264114 | Mgi Id | MGI:6191944 |
| Doi | 10.1242/dev.159103 | Citation | Mulas C, et al. (2018) Oct4 regulates the embryonic axis and coordinates exit from pluripotency and germ layer specification in the mouse embryo. Development 145(12):dev159103 |
| abstractText | 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. |
