Investigation of G protein receptor signaling for regenerative medicine.

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To utilize G protein signaling apparatus in regenerative medicine roles of G protein signaling during embryonic development and angiogenesis were explored. We were able to obtain following results.1. To inhibit Gi signaling in various cell types a mouse line that can express pertussi after removal of STOP cassette by Cre was developed. This line was used to block Gi signaling specifically in the vascular or nervous system. We found that Gi is critical for endocardial-mesenchymal transition in heart. In the nervous system Gi is required for neural tube closure in neuroepithelal cells. Ablation of Gi signaling in migrating neurons indicated the existence of important GPCRs in addition to CXCR4.2. As a downstream effecter of G protein signaling we focused RhoJ. Knocking out RhoJ or endothelial-specific overexpression revealed that RhoJ is required for the endothelial morphology change.