Presentation Information
[PT06-01]The role of oscillatory gene expression in embryogenesis
*Ryoichiro Kageyama1 (1. RIKEN Center for Brain Science (Japan))
Keywords:
Embryogenesis
The role of oscillatory gene expression in embryogenesis.
Many genes are expressed in an oscillatory manner in developmental processes, such as somitogenesis and neurogenesis. In mouse somitogenesis, Hes7 exhibits oscillatory expression with 2-hour periodicity and regulates periodic formation of somites. Hes7 oscillations are controlled by delayed negative feedback and delayed coupling; manipulation of these delays dampens Hes7 oscillations, leading to severe fusion of somites and somite-derived tissues such as the vertebrae and ribs. Similarly, Hes1 expression oscillates in embryonic neural stem cells (NSCs), which actively proliferate and generate neurons and glial cells. Hes1 oscillations periodically repress other cell fate determination factors such as the proneural gene Ascl1, thereby driving their oscillations. By using an optogenetic method, we found that oscillatory expression of these factors promotes proliferation of NSCs. Hes1 oscillations are also controlled by delayed negative feedback and delayed coupling, and manipulation of these delays dampens Hes1 oscillations, leading to microcephaly. Thus, oscillatory gene expression is required for proper developmental processes. I would also like to discuss the importance of mathematical modeling to deeper understanding of the mechanism of oscillatory gene expression.
Many genes are expressed in an oscillatory manner in developmental processes, such as somitogenesis and neurogenesis. In mouse somitogenesis, Hes7 exhibits oscillatory expression with 2-hour periodicity and regulates periodic formation of somites. Hes7 oscillations are controlled by delayed negative feedback and delayed coupling; manipulation of these delays dampens Hes7 oscillations, leading to severe fusion of somites and somite-derived tissues such as the vertebrae and ribs. Similarly, Hes1 expression oscillates in embryonic neural stem cells (NSCs), which actively proliferate and generate neurons and glial cells. Hes1 oscillations periodically repress other cell fate determination factors such as the proneural gene Ascl1, thereby driving their oscillations. By using an optogenetic method, we found that oscillatory expression of these factors promotes proliferation of NSCs. Hes1 oscillations are also controlled by delayed negative feedback and delayed coupling, and manipulation of these delays dampens Hes1 oscillations, leading to microcephaly. Thus, oscillatory gene expression is required for proper developmental processes. I would also like to discuss the importance of mathematical modeling to deeper understanding of the mechanism of oscillatory gene expression.