Use this URL to cite or link to this record in EThOS:
Title: Mechanical and geometric cues guiding early mammalian tissue development
Author: Leonavicius, Karolis
ISNI:       0000 0004 6500 6120
Awarding Body: University of Oxford
Current Institution: University of Oxford
Date of Award: 2016
Availability of Full Text:
Access from EThOS:
Full text unavailable from EThOS. Please try the link below.
Access from Institution:
Mammalian development is one of the most complex biological processes, that is responsible for converting a single cell into a whole organism. Al- though, mechanical forces are expected to play profound roles during de- velopment, proving the role of mechanical and geometric cues has been difficult due to the lack of suitable experimental techniques. The thesis investigates the hypothesis, that mechanical and geometric cues are driv- ing the first two cell fate decision events. In order to test them and create a robust experimental framework, the first three chapters are dedicated to developing methodology based on three dimensional patterned hydrogels. The hydrogels were mechanically and biochemically characterised in high detail and then used as three dimensional moulds to shape developing tis- sues. This technique also made it possible to calculate mechanical forces, which could be estimated from hydrogel deformation and known elastic properties. Finally, to characterise the biological outcomes of mechani- cal tissue deformation a heuristic confocal image analysis technique has been developed and used to investigate developing mammalian tissues. Using the techniques it was possible to demonstrate, that the first cell fate decision is controlled by embryo geometry and the molecular mecha- nism involved a complex combination of Hippo pathway signalling and a sequence of cell polarisation. Similarly, the second cell fate decision was also found to be driven by tissue geometry and Hippo pathway signalling, although the precise biochemical pathway was less clear.
Supervisor: Srinivas, Shankar ; Royer, Christophe ; Vollrath, Fritz Sponsor: BBSRC
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available