To construct complicated neural networks, glial cells migrate to their final destination to interact with neurons, either solitarily or in a group. Group or collective migration demands cell-cell communication as well as several intracellular mechanisms for reiterative processes during cell migration. In addition, collective behaviors imply dynamic and fine-tuning control of specific molecular pathways. Protein degradation by the ubiquitin proteasome system regulates key biological processes including cell cycle progression and signaling pathways. In a collaborative study between the two groups, we demonstrated that cullin-RING ubiquitin ligases (CRLs) regulate the protein levels of the glial fate determinant Gcm during Drosophila glial differentiation. We also made a preliminary observation that the protein degradation machinery impacts on glial migration. In addition, we have recently found that the levels of Gcm directly affect glial migration in a linear manner, that is, the more Gcm the more efficient the migration. Building upon these results, we propose to study the role of protein ubiquitination in collective migration using an in vivo model that is suitable for genetic analyses: the glial cell chain present in the Drosophila wing. The fast and precise control of protein levels/activity indeed makes the ubiquitination pathway an ideal candidate for the regulation of collective migration. On one side, the role of Gcm dosage in collective migration will be established by a live-imaging system. On the other side, the role of the ubiquitin proteasome system in collective glial migration will be studied to determine the involvement of specific degradation pathways. Genetic and biochemical studies will further elucidate how Gcm ubiquitination and degradation control collective glial migration. Finally, particular E3 ligases involved in collective glial migration will be identified. This collaborative proposal will be performed in both laboratories with the French group focusing on the live imaging and phenotypical analysis of the migration behaviors and the Taiwanese group on genetic and biochemical study of protein ubiquitination and degradation by E3 ligases. Videoconferences and bilateral lab meetings will be held regularly to monitor the progress and ensure the success of the collaboration. At the end of the collaborative grant, we will organize a symposium to promote interaction and collaboration for scientists from France and Taiwan. The project represents a revised application (BLI ANR 2011) that was very well perceived. The reviewers acknowledged the quality, the novelty and the originality of the proposed work. They also recognized the complementarity of the two teams and the fact that the proposed project stems form previous, collaborative work ("the two groups have completely complementary expertise so that neither the French nor the Taiwanese group could perform the proposed analysis on their own despite their excellent track records. The project therefore generates true added value. The consortium is unique in its expertise. Moreover, the consortium has already proven its effectiveness in the past as shown by their collaborative paper in PNAS in 2009"). The revised application complies with the request of a balanced effort and more exchanges between the two laboratories. In addition, a student Pei-Yi Chen, who is currently a master thesis student in National Yang Ming University, will work on this project. She will apply to PhD programs in both Taiwan and France and mentored by both PIs. Finally, a postdoc from the French group will stay in Taiwan for one year.