Encoding and decoding dynamic cell signaling: how to build a blood vessel

Dr. Andre Levchenko

Department of Biomedical Engineering and Systems Biology Institute, Yale University

Dynamics of cell signaling can carry important information about the environment and the potential responses to changes in this environment. Furthermore, a single extracellular stimulus can promote diverse behaviors among isogenic cells by differentially regulated signaling networks. We examined Ca2+ signaling in response to VEGF (vascular endothelial growth factor), a growth factor that can stimulate different behaviors in endothelial cells. We found that altering the amount of VEGF signaling in endothelial cells by stimulating them with different VEGF concentrations triggered distinct and mutually exclusive dynamic Ca2+ signaling responses that correlated with different cellular behaviors. These behaviors were cell proliferation involving the transcription factor NFAT (nuclear factor of activated T cells) and cell migration involving MLCK (myosin light chain kinase). Further analysis suggested that this signal decoding was robust to the noisy nature of the signal input. Ca2+ signaling patterns associated with proliferation and migration were detected during angiogenesis in developing zebrafish. In this talk, I will analyze how the signaling in the network can be balanced through diverse Ca2+ dynamics, and how this dynamics can be robustly decoded and converted into distinct behaviors needed to build a functional blood vessel.

Date: Aug. 06, 2018(Thr) 10:00—11:30
Place: Faculty of Science Bldg.3, 4F, room 412
Host: Shinya Kuroda(skuroda AT bs.s.u-tokyo.ac.jp)