The role of cellular memory modules in the determination and transdetermination of Drosophila melanogaster imaginal disc cells

The Polycomb-group (PcG) and trithorax-group (trxG) proteins ensure this function through their interplay at chromosomal elements, termed Cellular Memory Modules (CMMs), by creating stable and inheritable chromatin structures. By this way, CMMs are able to remember the embryonic state of transcription of homeotic genes and to maintain it throughout development. I asked whether such CMMs could also control expression of genes involved in patterning imaginal discs during larval development, which expression pattern may be modulated with time. The results demonstrate that expression of one of these genes, hedgehog, once activated, is maintained by a CMM even when the initial activator has disappeared. These experiments suggest that the chromatin-based epigenetic inheritance of gene expression involving CMMs may be widely spread. This implies that during imaginal disc patterning, the determination of a morphogenetic field is not only established by the surrounding combinations of signaling molecules but is also dependent from the history of the composing cells. Transdetermination is a switch of disc identity that occurs in some cells, under specific conditions, when cells are already determined. It was shown to appear in Drosophila when manually fragmented imaginal discs were cultivated for a period of time allowing several cell divisions. It is still unclear what factors are involved in the switch to the new identity and how cells are able to inherit it through cell divisions. I investigated the role of PcG and trxG genes in the determination and transdetermination of imaginal disc cells. My results show that reducing the concentration of some PcG members in the cells affects the frequency of transdetermination suggesting that some genes involved in the establishment of the new disc identity are targets of PcG-mediated regulation. Furthermore, PcG proteins may also be required for the accurate inheritance of the new transdetermined state through mitosis. These results suggest that the establishment and the maintenance of the new cell identity is generated through the switching of the activation state of the CMM of developmental genes. In conclusion, several conditions are defined that may favour or are necessary for transdetermination, in which a transient downregulation of some PcG/trxG proteins as well as several rounds of DNA replication may facilitate the switch of CMMs. Finally, I discuss these results with a perspective on how the control of CMM switching may have applications for medical research in tissue remodeling.

Level thesis:degree_level

thesis.doctoral

Grantor dc:publisher

Universität Heidelberg

Year

2002

Author dc:creator

• Maurange, Cedric

Contributors dc:contributor

• Paro, Renato

Repository record source_url

http://www.ub.uni-heidelberg.de/archiv/3083

OAI identifier oai:identifier

oai:archiv.ub.uni-heidelberg.de:3083