Notch Controls Cell Adhesion in the Drosophila Eye

Abstract

Sporadic evidence suggests Notch is involved in cell adhesion. However, the underlying mechanism is unknown. Here I have investigated an epithelial remodeling process in the Drosophila eye in which two primary pigment cells (PPCs) with a characteristic ‘kidney’ shape enwrap and eventually isolate a group of cone cells from inter-ommatidial cells (IOCs). This paper shows that in the developing Drosophila eye the ligand Delta was transcribed in cone cells and Notch was activated in the adjacent PPC precursors. In the absence of Notch, emerging PPCs failed to enwrap cone cells, and hibris (hbs) and sns, two genes coding for adhesion molecules of the Nephrin group that mediate preferential adhesion, were not transcribed in PPC precursors. Conversely, activation of Notch in single IOCs led to ectopic expression of hbs and sns. By contrast, in a single IOC that normally transcribes rst, a gene coding for an adhesion molecule of the Neph1 group that binds Hbs and Sns, activation of Notch led to a loss of rst transcription. In addition, in a Notch mutant where two emerging PPCs failed to enwrap cone cells, expression of hbs in PPC precursors restored the ability of these cells to surround cone cells. Further, expression of hbs or rst in a single rst- or hbs-expressing cell, respectively, led to removal of the counterpart from the membrane within the same cell through cis-interaction and forced expression of Rst in all hbs-expressing PPCs strongly disrupted the remodeling process. Finally, a loss of both hbs and sns in single PPC precursors led to constriction of the apical surface that compromised the ‘kidney’ shape of PPCs. Taken together, these results indicate that cone cells utilize Notch signaling to instruct neighboring PPC precursors to surround them and Notch controls the remodeling process by differentially regulating four adhesion genes.

Cell Adhesion in the Assembly of theDrosophilaEye

“…A clear example is shown in the Drosophila eye. Initially IRM adhesion molecules are present in all epithelial cells in the early pupal eye (Bao, 2014). As described earlier, during the selection of PPCs, cone cells send Notch signaling to emerging PPC precursors (Figure 2).…”

“…An early sign of asymmetry comes from Delta (Dl), a ligand of Notch. Around 18 h APF, Dl is differentially expressed in cone cells: the Dl expression level is higher in anterior-posterior than in polarequatorial cone cells (Bao, 2014). Consistently, Notch activity is higher in cells adjacent to anterior-posterior cone cells than others.…”

“…Notch activates transcription of hbs and sns, genes coding for IRM adhesion molecules of the Nephrin group, whereas it represses rst and kirre genes of the Neph1 group. Cis-interactions between Hbs/ Sns and Rst/Kirre further facilitate removal of remnant Rst/Kirre proteins from emerging PPCs and Hbs/Sns from IOCs (Bao, 2014). As a result, Hbs and Sns are expressed in emerging PPCs, whereas Rst and Kirre by default are constantly produced by IOCs.…”

“…Second, Hbs and Sns are required for organization of cone cells and PPCs. In emerging PPCs, Rst and Kirre are phasing out (Bao, 2014). Hbs and Sns are known to mediate heterophilic interaction with Rst and Kirre, IRM adhesion molecules of the Neph1 group (Bao & Cagan, 2005;Bao et al, 2010).…”

The vav oncogene antagonises EGFR signalling and regulates adherens junction dynamics during Drosophila eye development

“…Recently, with the development of live imaging tools, the use of the Drosophila eye has proven to be an excellent system to study the role of adhesion and junction dynamics in vivo (Larson et al, 2008). In particular, the recruitment of primary cells depends on both the integration of combinatorial signalling pathways (Nagaraj and Banerjee, 2007) and the regulation of cell-cell adhesion (Bao, 2014). Once the first two primary cell candidates are selected, they have to form stable junctions that enwrap the CCs and isolate them to prevent additional primary cell recruitment from the IPC pool.…”