Delta-like 4 is indispensable in thymic environment specific for T cell development

• DOI: 10.1084/jem.20080134
• Publication Date: 2008-09-30T00:54:14Z
• Authors: Katsuto Hozumi; Carolina Mailhos; Naoko Negishi; Ken-ichi Hirano; Takashi Yahata; Kiyoshi Ando; Saulius Zuklys; Georg A. Holländer; David T. Shima; Sonoko Habu
• Keywords: Lymphopoiesis; Cell fate determination; Compartment (ship)

The thymic microenvironment is required for T cell development in vivo. However, vitro studies have shown that when hematopoietic progenitors acquire Notch signaling via Delta-like (Dll)1 or Dll4, they differentiate into the lineage absence of a microenvironment. It not clear, however, whether thymus supports specifically by providing signaling. To address this issue, we generated mice with loxP-flanked allele Dll4 and induced gene deletion epithelial cells (TECs). In mutant mice, expression was abrogated on epithelium, proportion bearing intracellular fragment Notch1 (ICN1) markedly decreased. Corresponding to this, CD4 CD8 double-positive single-positive were detected thymus. Further analysis showed double-negative fraction lacking progenitors. enforced ICN1 restored differentiation, even TECs deficient Dll4. These results indicate thymus-specific environment determining fate indispensably requires induce immigrant cells.