Unveiling the mechanisms through which the somitogenesis regulatory network exertsspatiotemporal control of the somitic patterning has required a combination ofexperimental and mathematical modeling strategies. Significant progress has been made forthe zebrafish clockwork. However, due to its complexity, the clockwork of the amniotesegmentation regulatory network has not been fully elucidated. Here, we address thequestion of how oscillations are arrested in the amniote segmentation clock. We do this byconstructing a minimal model of the regulatory network, which privileges architecturalinformation over molecular details. With a suitable choice of parameters, our model isable to reproduce the oscillatory behavior of the Wnt, Notch and FGF signaling pathways inpresomitic mesoderm (PSM) cells. By introducing positional information via a single Wnt3agradient, we show that oscillations are arrested following an infinite-period bifurcation.Notably: the oscillations increase their amplitude as cells approach the anterior PSM andremain in an upregulated state when arrested; the transition from the oscillatory regimeto the upregulated state exhibits hysteresis; and opposing Fgf8 and RA gradients along thePSM naturally arise in our simulations. We hypothesize that the interaction between alimit cycle (originated by the Notch delayed-negative feedback loop) and a bistable switch(originated by the Wnt-Notch positive cross-regulation) is responsible for the observedsegmentation patterning. Our results agree with previously unexplained experimentalobservations and suggest a simple plausible mechanism for spatiotemporal control ofsomitogenesis in amniotes.

We have been involved with a group of computer scientists and anatomists in the development of computer-based methodologies that not only combine the advantages of scanning electron microscopy and conventional histology, but provide the additional dimension of tissue recognition. The latter is achieved by the appropriate labelling of tissues and structures by delineation or ‘painting’. Individually segmented anatomically defined tissues can be highlighted in a particular colour and viewed either in isolation or in combination with other appropriately labelled tissues and organs. Tissues can be shown in any orientation either as a transparent overlay on computer-generated histological sections or as 3-D images without the histological background. An additional feature of the system is that computer graphics technology combined with 3-D glasses now also allows the viewer to see the object under analysis in stereo. This facility has been found to be particularly helpful in drawing attention to topological relationships that had not previously been readily noted. As the mouse is now the mammalian model of choice in many areas of developmental research, it is of critical importance that a basic level of skill is available in the research community in the interpretation of serially sectioned material, for example, for the rapidly expanding field in which gene expression studies play a significant role. It is equally important that there is an understanding of the dynamic changes that occur in relation to the differentiation of the various organ systems seen in these early stages of development. What we emphasise here is the additional information that it is possible to gain from the use of this tool which, in our view, could not readily have been gained from the analysis of scanning electron micrographs or by studying conventional serial histological sections of similar stages of mouse embryonic development. The methodology has been developed as part of a large project to prepare a database of mouse developmental anatomy covering all stages from fertilisation to birth in order to allow the accurate spatial mapping of gene expression and cell lineage data onto the digital Atlas of normal mouse development. In this paper we show how this digital anatomical Atlas also represents a valuable teaching aid and research tool in anatomy.