Core binding factors are necessary for natural killer cell development and cooperate with Notch signaling during T-cell specification

Blood. 2008 Aug 1;112(3):480-92. doi: 10.1182/blood-2007-10-120261. Epub 2008 Apr 4.


CBFbeta is the non-DNA binding subunit of the core binding factors (CBFs). Mice with reduced CBFbeta levels display profound, early defects in T-cell but not B-cell development. Here we show that CBFbeta 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 CBFbeta insufficient cells, nor can overexpression of Runx1 or CBFbeta overcome a lack of Notch signaling. Therefore, the ability of the prethymic cell to respond appropriately to Notch is dependent on CBFbeta, and both signals converge to activate the T-cell developmental program.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Lineage
  • Core Binding Factor beta Subunit / deficiency
  • Core Binding Factor beta Subunit / physiology*
  • GATA3 Transcription Factor / deficiency
  • Hepatocyte Nuclear Factor 1-alpha
  • Killer Cells, Natural / cytology*
  • Lymphopoiesis*
  • Mice
  • Mice, Inbred C57BL
  • Receptors, Notch / physiology*
  • Signal Transduction
  • T Cell Transcription Factor 1 / deficiency
  • T-Lymphocytes / cytology*


  • Cbfb protein, mouse
  • Core Binding Factor beta Subunit
  • GATA3 Transcription Factor
  • Hepatocyte Nuclear Factor 1-alpha
  • Hnf1a protein, mouse
  • Receptors, Notch
  • T Cell Transcription Factor 1