SOX-4 FACILITATES THYMOCYTE DIFFERENTIATION

The mouse Sry-like transcription factor Sox-4 is expressed in thymus, bone marrow, and gonads of adult mice. Sox-4-deficient mice die at emb ryonic day E14 due to cardiac malformation. In transfer experiments to irradiated recipients, B cell development was shown to be severely im paired in Sox-4-deficient progenitor cells. However, no drastic effect s on T lymphocyte development were noted, despite the high level expre ssion of the Sox-4 gene in the thymus of normal mice. Here. we report a detailed analysis of T cell development from Sox-4-deficient progeni tors. Explanted fetal thymic organ cultures (FTOC) of Sox-4-deficient thymi yielded 10-50-fold fewer CD4 CD8 double-positive and single-posi tive cells than FTOC of littermates. This effect was T cell-autonomous , since similar observations were made when FTOC were performed by cul turing of Sox-4-deficient progenitors in wild-type thymus lobes. When Sox-4-deficient fetal liver cells were injected together with normal c ells intrathymically, they did not compete efficiently for reconstitut ion. It is concluded that Sox-4 facilitates thymocyte development.