Gastrulation is a key milestone in the development of an organism. It is a period of cell proliferation and coordinated cellular rearrangement, that creates an outline of the body plan. Our current understanding of mammalian gastrulation has been improved by embryo culture, but there are still many open questions that are difficult to address because of the intrauterine development of the embryos and the low number of specimens. In the case of humans, there are additional difficulties associated with technical and (...) ethical challenges. Over the last few years, pluripotent stem cell models are being developed that have the potential to become useful tools to understand the mammalian gastrulation. Here we review these models with a special emphasis on gastruloids and provide a survey of the methods to produce them robustly, their uses, relationship to embryos, and their prospects as well as their limitations. (shrink)

Wnt proteins are involved in a large number of events during development and disease. The crucial element in the transduction of the signal elicited by Wnt is the state and activity of β-catenin. There are two pools of β-catenin, one associated with cadherins at the cell surface and a soluble one in the cytolasm, whose state and concentration are critical for Wnt signalling. In the absence of Wnt, the cytoplasmic pool is low due to targetted degradation of β-catenin. Upon Wnt (...) signalling, β-catenin is stabilized. As a consequence, it can access the nucleus where it interacts with members of the Tcf family of transcription factors to modulate the expression of defined targets. Recent reports indicate that, in addition to Tcfs, β-catenin can interact with other nuclear proteins raising the possibility that Wnt signalling has a wider modulatory effect on transcription than is mediated by its interactions with Tcfs. BioEssays 23:311–318, 2001. © 2001 John Wiley & Sons, Inc. (shrink)

The activity of Wnt and Notch signalling is central to many cell fate decisions during development and to the maintenance and differentiation of stem cell populations in homeostasis. While classical views refer to these pathways as independent signal transduction devices that co‐operate in different systems, recent work has revealed intricate connections between their components. These observations suggest that rather than operating as two separate pathways, elements of Wnt and Notch signalling configure an integrated molecular device whose main function is to (...) regulate transitions between cell states in development and homeostasis. Here, we propose a general framework for the structure and function of the interactions between these signalling systems that is focused on the notion of ‘transition states’, i.e. intermediates that arise during cell fate decision processes. These intermediates act as checkpoints in cell fate decision processes and are characterised by the mixed molecular identities of the states involved in these processes.Editor's suggested further reading in BioEssays: Notch: Implications of endogenous inhibitors for therapy Abstract. (shrink)