MBI PhD Oral Defence

Time: 12PM
Date: Monday, 20 January 2020
Venue: T-Lab Building, Level 5 Meeting Room 1

Supervisor: Prof. Timothy SAUNDERS

DECIPHERING THE DYNAMIC REGULATIONS OF THE PRECISE CELL MATCHING

by ZHANG Shaobo, Saunders Group

It has been an age-old question about the embryo development: how the cells find their partners correctly in a complicated as well as dynamic cellular environment? In the past, studies from neurogenesis have found various molecules being important in this cell matching process. However, the underlying mechanisms, especially the dynamics, remain elusive. Here, we explored this by applying the cardiogenesis in the Drosophila embryo as a simplified matching system. The formation of the Drosophila heart involves a long range of cell migration but results in robustly formed cell-partner connections. By fast in vivo live imaging, we found that cell matching is particularly robust at boundaries between cardioblast (CB) subtypes of which their filopodia show distinct binding affinities. Through genetic screening, we identified the adhesion molecules Fas3 and Ten-m, both of which also regulate synaptic targeting, as having complementary expression patterns in CBs. Altering Fas3 or Ten-m expression changes differential filopodia adhesion and leads to CB mismatch. Further, focusing on Myosin II, showing ‘wave’ like dynamics within the CBs, we found that coordination between Myosin II oscillations within CBs and differential filopodia connectivity between CBs is essential in ensuring robust cell matching. By using genetic manipulations and laser ablation, we have found that the CB filopodia activity is highly Myosin II dependent. It appears that the Myosin II oscillation acts as a “mechanical proof-reader” of cell-cell connections, whereby weak connections are broken and strong ones reinforced. Altering Myosin II activity – either by over-activation or inhibition of Myosin II – results in perturbed cell matching. Additionally, changing the Myosin II oscillation pattern also leads to misaligned CBs. Combined, these results suggest that the mechanical properties of cells are precisely tuned to provide a ‘proofreading’ machinery to ensure robust cell matching.

**Please note the examination following the seminar is closed-door**