MBI PhD Oral Defense

Time: 3pm
Date:  Monday, 15 October 2018
Venue: NUS Faculty of Engineering, E3-06-14

Supervisors: Prof Timothy Saunders (Main supervisor)

A multi-scale study of somitic cell differentiation and somite morphogenesis

by YIN Jianmin, Saunders Group

During development, numerous cell types and diverse patterns are induced through combinations of inputs from a limited number of signaling pathways. Extensive studies in the past several decades have revealed the great importance of precise spatio-temporal control of the signaling pathway activities in rendering cells with unique positional information. However, positional information must often be conveyed to cells whilst morphogenesis and migration are also occurring. In this study, we explored the participation of cell morphogenesis and cell migration in the cell fate determination by studying the primary myogenesis of Zebrafish somite, in which somitic cells giving rise to slow and fast-twitch muscle fibers, dermomyotome, and non-muscle progenitors. The rapid cell morphogenesis and cell migration have, to date, impeded the understanding of the patterning of somite. It remains largely unknown how, where, and when these different cell fates are specified within the somite.

We utilized whole-somite 4D live imaging and cell tracking to systemically reveal the niches of somitic descendants. Our data demonstrated that somite patterning is underpinned by a series of highly organized and directional cell morphogenesis and cell migration events. These highly orchestrated cellular behaviors ensure robust somite compartmentalization by allocating cells at specific locations relative to the signaling center.

We systematically studied the roles of FGF signaling pathways in the differentiation of slow and fast muscles. Our data demonstrated that FGF directly and indirectly controls the differentiation of fast and slow- twitch muscle lineages respectively. The non-autonomous FGF signaling imposes tight temporal control on the Shh/BMP activation/repression of slow muscles through regulating the time at which fast-twitch progenitors displace slow muscles from contacting the Shh-secreting notochord. Further, we explored the interactions between different somitic populations: the myogenesis of fast muscle progenitors is required for the lateral migration of slow muscle; the migrating slow muscle fibres reciprocally regulate the myogenesis and morphogenesis of the fast muscle fibers.

This thesis demonstrates the great importance of the spatio-temporal coordination between cell migration and cell fate determination in the patterning of complicated tissues and organs. A multiple scale study with in toto live imaging approach combined with multiple genetic perturbations was proved to be practical in resolving the patterning of complicated tissues in this study.

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