IMSc Webinar

Contact-mediated signaling in developmental pattern formation

K A Chandrashekar

IMSc, Chennai

Development of an organism from the embryonic stage involves a number of precisely timed events that arise as a result of interactions between several components including (i) morphogens which set up concentration gradients, (ii) cell-cycle oscillators which regulate mitosis and (iii) inter-cellular communication. While the role of morphogens has received enormous attention in developmental contexts, it is now becoming clear that juxtacrine signaling, which occurs between cells in physical proximity, can also play a key role in shaping the outcomes of such processes. The aim of the PhD thesis, for which this is a pre-synopsis submission talk, is to investigate the precise mechanism by which contact-mediated signaling affects specific developmental phenomena. In particular, the Notch receptor-Delta ligand communication between neighboring cells is shown to play a hitherto unexpected role in the ``French Flag'' paradigm, which describes how a morphogen concentration gradient can dictate different cell fates in a position-dependent manner. This is followed by showing that the same inter-cellular communication mechanism can change the collective behavior of oscillatory gene expression (involving so-called ``clock genes'') thereby reproducing all the empirically observed dynamical transitions in somitogenesis, a fundamental developmental process in all vertebrates. Finally, it is shown that coupling cell-cycle oscillators in a tissue via contact-induced signals can lead to arrest of further growth of an organ once it reaches an appropriate size. It is shown that the changing geometry of cellular packing over the course of development results in altering the intensity of the contact-induced signal, a mechanism that when impaired can lead to developmental pathologies including cancer.
meet.google.com/vnb-bryo-fbd