Research

 

“Science does not deal in compromises but in discoveries. When we say the development of the egg is inherent, must we not also say what are the relations to which it is inherent? If we say it is induced, must we not also say what are the relations with reference to which it is induced?”

– W.K. Brooks (1902)

Pattern formation in development is often seen as a product of global signalling mechanisms generating pattern across a particular tissue, which is then read by gene regulatory networks that result in changes to a cell’s cell fate and/or movement (scheme A, below). However, given the dynamic nature of developmental processes, it is difficult to understand how such global patterns can be mapped onto a cellular substrate that is constantly shifting. For example, the basic body plan with anterior-posterior and dorsal-ventral axes are established during gastrulation, when massive convergence and extension movements are constantly shifting cells in their spatial relationship to one another. How can simple cartesian coordinated be mapped onto such a dynamic structure?

Rather than understanding pattern formation as a static read-out of global signalling mechanisms, I prefer to understand pattern formation as an emergent property of a dynamic system (scheme B, below). In this framework, coupling of transitions in gene regulatory network state together with their spatial position within the tissue of interest is achieved by signalling. By linking these two processes in such a manner, pattern forms over time. This not only has the potential to explain how pattern forms during the complex movements of gastrulation, but also how seemingly conserved molecular mechanisms have been utilised in the patterning of the body axis of organisms with vastly different geometries.

patterningTo investigate this hypothesis, an experimental system is required in which we can probe gene regulatory states and cell movements with single cell resolution during the establishment of the body axis, and to be able to compare this across experimental models that differ in their geometry. Therefore, we focus of the development of a bipotent population of stem cells called neuromesodermal progenitors. This essential cell population continues to provide progenitors for both the spinal cord and mesodermal during elongation of the posterior body axis. Their cell population dynamics must be precisely altered between vertebrate species in order to generate homologous body plans that differ vastly in their number of segments and the degree of growth that occurs concomitantly with axis elongation and somitogenesis.

We are now in an exciting position to explore the role of the endogenous signalling environment in the dynamics of this process. By applying dynamic and single cell studies in zebrafish will allow for a platform upon which to understand how cell fate specification has been precisely balanced to generate a well proportions body axis.

By extending these studies to other vertebrates such as mice and chick, we can then begin to understand how a self-renewing stem cell pool has been generated within these organisms to accomodate the increased growth that occurs concomitantly with the generation of the body axis. Finally, by performing multi-scalar analyses of morphogenesis, we are gaining a more complete picture of how cellular behaviours generate elongation of the posterior body. This is an example of complex morphogenesis, in which multiple tissues undergo a range of deformations into order to generate elongation at the level of the whole axis.