The Hox timer: Evolution, Function and Mechanism: Jenkinson Memorial Lecture

Understanding how developmental time is encoded in genomes is a major challenge, either for mechanisms acting in trans (e.g., oscillations) or for those acting in cis. In the latter category, clustered Hox genes are activated during development in a precise time-sequence that follows the linearity of the DNA polymer. 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.

Professor Duboule will discuss 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 insulating elements. In this view, the directionality and processivity of the mechanism are fixed by the asymmetric over-loading of cohesin complexes at one extremity of the gene cluster. While this mechanism can secure the sequential 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 offering possibilities for morphological evolution.

After-lecture drinks reception in the Illy Café, Oxford Martin School – 17:15-18:30