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SUMMARY:Milstein Lecture 2023: Understanding the Hox timer by Using mammal
 ian Pseudo-Embryos - Denis Duboule\, Collège de France\, Paris France\, F
 ederal Institute of Technology (EPFL)\, Lausanne\, Switzerland
DTSTART:20230126T103000Z
DTEND:20230126T113000Z
UID:TALK193975@talks.cam.ac.uk
CONTACT:Scientific Meetings Co-ordinator
DESCRIPTION:Understanding how developmental time is encoded in genomes is 
 a major challenge\, either for mechanisms acting in trans (e.g.\, oscillat
 ions) of for those acting in cis. In the latter category\, clustered Hox g
 enes are activated during development in a precise time-sequence that foll
 ows the linearity of the DNA polymer. The mechanism underlying this in cis
  timing phenomenon (the Hox timer)\, which is implemented throughout the n
 eck of the ‘developmental hourglass’\, has remained elusive ever since
  its initial observation in 1989\, due to the difficulty to approach it us
 ing early gastrulating mouse embryos. \nI will discuss recent results usin
 g pseudo-embryos produced out of ES cells (‘gastruloids’) as an altern
 ative approach to address this question and will show that the temporal dy
 namic of the system may rely upon the use of series of CTCF sites as succe
 ssive insulating elements. In this view\, the directionality and processiv
 ity of the mechanism are fixed by the asymmetric over-loading of cohesin c
 omplexes at one extremity of the gene cluster. While this mechanism can se
 cure the sequential deployment of Hox gene transcription and hence the pro
 per 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 evolu
 tion.
LOCATION:In person in the Max Perutz Lecture Theatre (CB2 0QH) 
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