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.
I 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.
Speaker: Professor Denis Duboule
Denis Duboule studied biology in Geneva and obtained a PhD in mammalian embryology in 1984. He was then a group leader in Strasbourg (France) and at the European Laboratory for Molecular Biology (EMBL) in Germany. In 1993, he was appointed Full Professor at the university of Geneva where he chaired the Dept of Genetics and Evolution for 20 years. Since 2006 he is also professor at the federal institute of technology (EPFL) in Lausanne and at the Collège de France in Paris since 2018.
His research is in the fields of embryology, genetics and developmental genomics, in an evolutionary context. Duboule has received numerous scientific prizes and decorations and is member of the Academia Europea and of several European academies including the French academy of Sciences. He is a foreign member of the Royal Society and of the National Academy of Sciences USA.
After-lecture drinks reception in the Illy Café, Oxford Martin School – 17:15-18:30
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