Milstein Lecture 2023: Understanding the Hox timer by Using mammalian Pseudo-Embryos

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• Denis Duboule, Collège de France, Paris France, Federal Institute of Technology (EPFL), Lausanne, Switzerland
• Thursday 26 January 2023, 10:30-11:30
• In person in the Max Perutz Lecture Theatre (CB2 0QH) .

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Understanding how developmental time is encoded in genomes is a major challenge, either for mechanisms acting in trans (e.g., oscillations) of 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.

This talk is part of the MRC LMB Seminar Series series.

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