'Synthetic' embryos and the mechanism of the Hox timer
During vertebrate development, clustered Hox genes are activated in a precise time-sequence, leading to patterns necessary to properly establish the body plan. The mechanism underlying this in cis timing phenomenon (the Hox timer), which is implemented throughout the neck of the developmental hourglass, has remained elusive ever since its initial observation in 1989, due to the difficulty to approach it using early gastrulating mouse embryos. I will discuss our recent results using pseudo-embryos produced out of ES cells (‘gastruloids’) as an alternative approach to address this question and will show that the temporal dynamic of the system may rely upon the use of series of CTCF sites as successive boundary elements, the directionality of the mechanism being fixed by the asymmetric loading of cohesin complexes. While this mechanism can secure the deployment of Hox gene transcription and hence the proper establishment of axial structures within any given vertebrate species, it also offers some evolutionary flexibility, for minimal modifications in the number, position or affinity of these sites would translate into heterochronic transcription.