Submitted October 29, 2007
Accepted March 13, 2008
Core binding factors are necessary for natural killer cell development, and cooperate with Notch signaling during T cell specification
Yalin Guo, Ivan Maillard, Sankhamala Chakraborti, Ellen V. Rothenberg, and Nancy A. Speck*
Department of Biochemistry, Dartmouth Medical School, Hanover, NH, United States
Division of Hematology-Oncology, University of Michigan, Ann Arbor, MI, United States
Division of Biology, California Institute of Technology, Pasadena, CA, United States
* Corresponding author; email: nancy.speck{at}dartmouth.edu.
CBF
is the non-DNA binding subunit of the core binding factors (CBFs). Mice with reduced CBF levels display profound, early defects in T but not B cell development. Here we show that CBF is also required at very early stages of natural killer (NK) cell development. We also demonstrate that T cell development aborts during specification, as the expression of Gata3 and Tcf7, which encode key regulators of T lineage specification, is substantially reduced, as are functional thymic progenitors. Constitutively active Notch or IL-7 signaling cannot restore T cell expansion or differentiation of CBF insufficient cells, nor can overexpression of Runx1 or CBF overcome a lack of Notch signaling. Therefore the ability of the prethymic cell to respond appropriately to Notch is dependent on CBF, and both signals converge to activate the T cell developmental program.
