Investigating the role of the teneurin Ten-M in planar polarisation of Myosin II during Drosophila axis extension

Theme: World-Class Underpinning Bioscience

During the initial stages of development in metazoa, a single population of cells is split into a series of separate sub-populations. The fate of each sub-population is determined by a variety of patterning and differentiation signals, which alter the gene regulatory networks within cells. Therefore, each group of cells develops a distinct identity and function, enabling a diverse range of tissue types to arise from a single original mass of cells. (Francois Fagotto 2015). Tissue boundaries present within the developing organism prevent distinct groups of cells from mixing, and ensure cells maintain a specific spatial position in the embryo so they receive the correct regulatory signals throughout development.

Within metazoan organisms, a variety of different boundary types are present. Inter-tissue boundaries physically separate different types of tissue. Alternately, intra-tissue boundaries also exist, which separate distinct groups of cells within a single tissue. In comparison, compartmental boundaries prevent cells of distinct lineage from mixing within the tissue.

One of the underlying questions regarding compartmental boundaries was how the boundary physically restricts the mixing of cells. A role for actomyosin enrichment at the boundary emerged from studies at the D-V boundary of the Drosophila wing disc, where F- actin and myosin II were shown to be enriched at the level of the adherens junction (Major and Irvine 2005; Major and Irvine 2006). Further, at the wing disc A-P boundary, laser ablation showed the mechanical tension at this interface is 2.5-fold higher than at other interfaces within the wing (Landsberg et al. 2009). However, the physical mechanism preventing the mixing of cells across a boundary was first shown at Drosophila germ-band parasegmental boundaries (PSBs), where the removal of myosin II using chromophore- assisted laser inactivation (CALI), caused proliferating cells to disrupt the sharp boundary. It was also shown that an actomyosin cable runs alongside the boundary, connecting between juxtaposing cells through adherens junctions, which establishes tension and restricts cell mixing (Monier et al. 2010). In vertebrates, a similar role for an actomyosin cable has been shown at compartmental boundaries separating Zebrafish rhombomeres (Calzolari, Terriente, and Pujades 2014). In terms of regulation of actomyosin enrichment, Wingless signalling is required for maintenance of PSBs whilst Notch signalling maintains the D-V wing disc boundary (Monier et al. 2010; Major and Irvine 2005; Dahmann, Oates, and Brand 2011).

Aims of the Project:
1. Identify the combination of cell surface receptors responsible for the formation of parasegmental boundaries and the correct sorting of cells during axis extension in Drosophila.
2. Investigate whether differences in cell identity, as defined by cell surface receptor expression levels, facilitates actomyosin enrichment in the germ-band.
3. Explore the molecular mechanism of actomyosin recruitment to PSBs.