ABSTRACT
The anterior-posterior axis of the mammalian embryo is laid down by the anterior visceral endoderm (AVE), an extraembryonic signaling center that is specified within the visceral endoderm. Current models posit that AVE differentiation is promoted globally by epiblast-derived Nodal signals, and spatially restricted by a BMP gradient established by the extraembryonic ectoderm. Here, we report spatially restricted AVE differentiation in bilayered embryo-like aggregates made from mouse embryonic stem cells that lack an extraembryonic ectoderm. Notably, clusters of AVE cells also form in pure visceral endoderm cultures upon activation of Nodal signaling, indicating that tissue-intrinsic factors can restrict AVE differentiation. We identify ß-catenin activity as a tissue-intrinsic factor that antagonizes AVE-inducing Nodal signals. Together, our results show how an AVE-like population can arise through interactions between epiblast and visceral endoderm alone. This mechanism may be a flexible solution for axis patterning in a wide range of embryo geometries, and provide robustness to axis patterning when coupled with signal gradients.
Subject(s)
Body Patterning , Cell Differentiation , Endoderm , Nodal Protein , Signal Transduction , beta Catenin , Animals , Endoderm/cytology , Endoderm/metabolism , Endoderm/embryology , beta Catenin/metabolism , Mice , Nodal Protein/metabolism , Nodal Protein/genetics , Germ Layers/metabolism , Germ Layers/cytology , Mouse Embryonic Stem Cells/metabolism , Mouse Embryonic Stem Cells/cytology , Gene Expression Regulation, Developmental , Embryo, Mammalian/cytologyABSTRACT
Combined awareness about the power and limitations of bioinformatics and molecular biology enables advanced research based on high-throughput data. Despite an increasing demand of scientists with a combined background in both fields, the education of dry and wet lab subjects are often still separated. This work describes an example of integrated education with a focus on genomics and transcriptomics. Participants learned computational and molecular biology methods in the same practical course. Peer-review was applied as a teaching method to foster cooperative learning of students with heterogeneous backgrounds. The positive evaluation results indicate that this approach was accepted by the participants and would likely be suitable for wider scale application.
