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The early mouse embryo is an excellent system to study how a small group of initially rounded cells start to change shape and establish the first forms of adhesion-based cell-cell interactions in mammals in vivo. In addition to its critical role in the structural integrity of the embryo, we discuss here how adhesion is important to regulate cell polarity and cell fate. Recent evidence suggests that adherens junctions participate in signaling pathways by localizing key proteins to subcellular microdomains. E-cadherin has been identified as the main player required for the establishment of adhesion but other mechanisms involving additional proteins or physical forces acting in the embryo may also contribute. Application of new technologies that enable high-resolution quantitative imaging of adhesion protein dynamics and measurements of biomechanical forces will provide a greater understanding of how adhesion patterns the early mammalian embryo., (© 2015 Elsevier Inc. All rights reserved.)

The preimplantation mouse embryo is a simple self-contained system, making it an excellent model to discover how mammalian cells function in real time and in vivo . Work over the last decade has revealed some key morphogenetic mechanisms that drive early development, yielding rudimentary instructions for the generation of a mammalian embryo. Here, we review the instructions revealed thus far, and then discuss remaining challenges to discover upstream factors controlling cell fate determination, test the role of mechanisms based on biological noise, and take advantage of recent technological developments to advance the spatial and temporal resolution of our current understanding. [ABSTRACT FROM AUTHOR]

Wnt signaling is a critical determinant of cell lineage development. This study used Wnt dose-dependent induction programs to gain insights into molecular regulation of stem cell differentiation. We performed single-cell RNA sequencing of hiPSCs responding to a dose escalation protocol with Wnt agonist CHIR-99021 during the exit from pluripotency to identify cell types and genetic activity driven by Wnt stimulation. Results of activated gene sets and cell types were used to build a multiple regression model that predicts the efficiency of cardiomyocyte differentiation. Cross-referencing Wnt-associated gene expression profiles to the Connectivity Map database, we identified the small-molecule drug, tranilast. We found that tranilast synergistically activates Wnt signaling to promote cardiac lineage differentiation, which we validate by in vitro analysis of hiPSC differentiation and in vivo analysis of developing quail embryos. Our study provides an integrated workflow that links experimental datasets, prediction models, and small-molecule databases to identify drug-like compounds that control cell differentiation. [Display omitted] • Wnt dose controls differentiation of mesendoderm gene programs and cell types • Multiple regression model predicts cardiac differentiation efficiency • Tranilast enhances differentiation by promoting mesoderm and suppressing endoderm • Tranilast synergistically promotes cardiac differentiation in vivo and in vitro Wu et al. use scRNA-seq to evaluate how Wnt signaling dose affects derivation of cell types from pluripotency. They build a computational model to identify a gene set predictive of cardiomyocyte differentiation and identify a small-molecule Wnt regulator, tranilast, that promotes cardiac differentiation both in vivo and in vitro. [ABSTRACT FROM AUTHOR]