Introduction: Collective cell migration is an important process during development, wound repair and metastasis. Border cells (BC) migration in Drosophila egg chamber is a powerful model to study collective cell migration in vivo. Misshapen (Msn) is a key regulator of this process that coordinates protrusion formation with contractile forces through the border cell cluster. However, the molecular mechanism regulating Msn in border cells is still unknown. Msn is composed of a kinase domain and a Citron homology (CNH) domain separated by a long coiled-coil. The kinase domain was shown to be phosphorylated by the kinase Tao in other contexts, while CNH domains are described to be bind to small GTPases. Therefore, our hypothesis is that both Tao and small GTPases regulate Msn activity during border cell migration. Methods and Results: Border cell clusters depleted for Tao or Msn are phenotypically identical: they do not entirely detach from the follicle epithelium and they present ectopic protrusions. Interestingly, the expression of a Msn phosphomimetic form restores the migration phenotype induced by Tao depletion. This indicates that the main function of Tao in BCs is to phosphorylate and activate Msn. Furthermore, we found that the CNH domain of Msn is required for its recruitment at the periphery of the cluster, suggesting that its interaction with a GTPase is required for its recruitment. Using the expression of mutant form of Rho and Rap GTPases and co-immunoprecipitation, we found that Rap1 and Rap2l might regulate Msn. In particular, we found that Msn binds preferentially to Rap2L. The role of Rap2L in BC migration is unknown, but preliminary data shows that its depletion induces a migration phenotype. Further analysis of the lost-of-function phenotype and its effects on Msn localization will be performed. Conclusion and Relevance: Here we presented two mechanisms of regulation of Msn in BC migration. We show that Tao acts as Msn upstream kinase to activate it in BC. Furthermore, we found that Msn binds to Rap GTPases with a preference to Rap2L, which might regulate its recruitment at the periphery of the BC cluster. The Msn ortholog, MAP4K4, is found dysregulated in many cancers and related to metastatic capacity and has been linked to Rap2 and Tao kinases. Therefore, our findings suggest that a conserved molecular cascade regulates the collective cell migration in BCs and during cancer progression.