The role of Cdc42 protein in thymocytes development and function

Abstract

Small Rho GTPases belong to the Ras superfamily, including RhoA, Rac1, and Cdc42. Rho-GTPases switch between inactive (GDP-bounded) and active (GTP-bounded) forms during signaling pathways. Cell division control protein 42 homolog (Cdc42) regulates the cell cycle, cell morphology, and migration. It activates WASP and Arp2/3 complex and has a role in actin polymerization that creates filopodia structures. In order to uncover the potential role of Cdc42 protein in T thymocytes development and function, Cdc42 loxP mice were bred with CD4 Cre mice to obtain Cdc42 knockout only in T cells. By comparing WT and cKO mouse T cells with flow cytometry assays and imaging techniques, the potential role of Cdc42 in T cell migration was investigated. In this study, It was confirmed that Cdc42 protein is required for full differentiation of TCR-αβ expressing SP thymocytes. From DP to SP stage, Cdc42 knockout cells were neglected by negative selection and led less SP4 and SP8 thymocytes populations. Deletion of the Cdc42 gene led to smaller thymocytes with fewer microvilli formation and TCR-β expression. Further, it was found that Cdc42 knockout generates abnormal T cell subsets in the periphery. In conclusion, Cdc42 knockout showed inadequate thymocytes development and leads to reduced antigen recognition.