Understanding how are tissues shaped during embryonic growth
During the embryonic growth and development of animals, thousands of cells organise themselves into tissues and organs with a variety of complex shapes.
I study early Drosophila embryos to understand the fundamental mechanisms by which tissues are shaped during embryonic development, a process called morphogenesis.
Studying the forces underlying morphogenesis
To fully understand morphogenesis, we must understand the nature of all the forces involved and how they act together to direct the final shape of a tissue (Lye and Sanson, 2011). Tissues arise from groups of cells, which undergo collective cell movements to generate the final shape of the tissue.
Cells in the group can generate their own, intrinsic, forces to drive genetically-programmed cell behaviours contributing to collective cell movement. Cells can also respond to physical forces generated elsewhere in the embryo (extrinsic forces), either by deforming passively or responding actively. I aim to address integration of both genetically-programmed and physical cues during collective cell movement, using Drosophila axis extension as a model.
I use genetics, in vivo imaging, cell tracking and computational analysis to analyse in detail how cells move and change shape during axis extension in order to understand the forces driving these cell behaviours.
Identifying novel proteins involved in morphogenesis
To identify proteins involved in generating the forces underlying morphogenesis, I led a screen of Drosophila exon-trap lines expressing YFP-tagged proteins, which had been generated by the Cambridge Protein Trap Insertion Team (Lowe et al, 2014; website). The Yellow Fluorescent Protein (YFP) tag allows the proteins to be visualized in living embryos. We characterized the subcellular localization of 600 YFP-tagged proteins in early Drosophila embryos (Lye et al, 2014). Specifically, we identified proteins localizing to the cortex of the cell, which is where the force generating cytoskeleton of the cell resides. The role of these proteins in morphogenesis is currently being assessed by members of the Sanson lab.
Lye C.M., Blanchard G.B., Naylor H.W., Muresan L., Huisken J., Adams R.J., Sanson B. Mechanical Coupling between Endoderm Invagination and Axis Extension in Drosophila. PLoS Biol. 2015 Nov 6;13(11):e1002292 pdf
Lye, C.M., Naylor, H.W., Sanson, B. (2014) Subcellular localisations of the CPTI collection of YFP-tagged proteins in Drosophila embryos. Development 141: 4006-4017. pdf
Lowe, N., Rees, J.S., Roote, J., Ryder, E., Armean, I.M., Johnson, G., Drummond, E., Spriggs, H., Drummond, J., Magbanua, J.P, Naylor, H., Sanson, B., Bastock, R., Huelsmann, S., Trovisco, V., Landgraf, M., Knowles-Barley, S., Armstrong, J.D., White-Cooper, H., Hansen, C., Roger G. Phillips, The UK Drosophila Protein Trap Screening Consortium*, Lilley, K.S., Russell, S., and St Johnston, D. (2014) Analysis of the expression patterns, subcellular localisations and interaction partners of Drosophila proteins using a pigP protein trap library Development 141: 3994- 4005. (*listed as author under Consortium list)
Lye, C., and Sanson, B. (2011) Tension and epithelial morphogenesis in Drosophila early embryos. Curr Top Dev Biol 95: 145-187.