Speaker: QIN Lei (Graduate Student, MBI, NUS)
Date: 30 November 2016, Wednesday
Time: 3pm
Venue: MBI, T-lab, level 5 seminar rooms
Supervisor(s): Asst. Prof Toyama Yusuke
Abstract: Collective cell migration is a common and essential multicellular process that occurs during animal development, tissue repair, and cancer metastasis. The regulation and underlying mechanism of collective cell migration is the key to our understanding of both normal physiological processes and abnormal pathologies. The current working model for collective cell migration is the “leader-follower” paradigm, in which leader cells are the force generator and major mechanical contributors for overall tissue movement. Comparing to the research focused on leader cells, there are fewer studies focused on follower cells whose functions and contributions in the collective cell migration are yet to be revealed.
In this study, live imaging combined with optogenetics was utilized to investigate follicle cell (FC) posterior migration during Drosophila middle oogenesis. While the FCs are composed of multiple subgroups, studying the collective migration of different subgroups during middle oogenesis serves as an ideal platform for the investigation of contributions from follower cells. Among all the FC subgroups, centripetal FCs were monitored and found to have the fastest migratory speed across the epithelium. This group of FCs was distributed, according to their marker gene Slbo, in a circumferential “band” pattern in the middle of the FC epithelium. Quantitative analyses of FC morphology and protein distribution along FC layers indicate a higher Rac and Ena accumulation on the apical surface of centripetal FCs. These accumulations have led to the appearance of dynamic protrusions and sharp apical angles in these cells. Moreover, suppression of endogenous Rac activity by photo-activatable dominant-negative (DN) Rac in different FC subgroups showed a significant role for centripetal FCs in FC posterior migration. Specifically, Rac suppression in centripetal FCs reduced migratory speed across the entire tissue. These results demonstrate a role for centripetal FCs in controlling FC migration, including generation of forces to push mainbody FCs in front of centripetal FCs, and forces to pull stretched FCs located behind. In addition, RNA interference (RNAi) studies reveal that the Rac-dependent migration of centripetal FCs was controlled by PVR/EGFR signaling, in response to the gurken ligand concentration gradient secreted from the posteriorly located oocyte.
In summary, this study uncovers the active contributions of centripetal FCs in FC posterior migration during Drosophila middle oogenesis. This is remarkable since centripetal FCs are located in the middle of the tissue and considered as “follower cells”, yet are equipped with higher migration ability in compared to surrounding cell types. They also act to physically push and pull neighboring cells for overall epithelial movement in response to the chemotactic signal generated by the oocyte. The work presented in this study will provide new insights into collective cell migration particularly in the context of contributions from follower cells, and fill the knowledge gap in the current “leader-follower” model.
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