T/B lineage choice occurs prior to intrathymic Notch signaling

• Published in: Blood Vol. 106; no. 3; pp. 886 - 892
• Main Authors: Harman, Benjamin C., Jenkinson, William E., Parnell, Sonia M., Rossi, Simona W., Jenkinson, Eric J., Anderson, Graham
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01.08.2005
• Subjects: Animals; B-Lymphocytes - cytology; B-Lymphocytes - physiology; Cell Communication; Cell Lineage; Coculture Techniques; Epithelial Cells - cytology; Epithelial Cells - physiology; Fetus; Liver - cytology; Liver - embryology; Membrane Proteins - physiology; Mice; Mice, Inbred BALB C; Mice, Knockout; Phosphatidylinositol-3,4,5-Trisphosphate 5-Phosphatases; Phosphoric Monoester Hydrolases - deficiency; Phosphoric Monoester Hydrolases - genetics; Receptors, Notch; Stromal Cells - cytology; Stromal Cells - physiology; T-Lymphocytes - cytology; T-Lymphocytes - physiology; Thymus Gland - cytology
• ISSN: 0006-4971; 1528-0020
• DOI: 10.1182/blood-2004-12-4881

Commitment of hemopoietic progenitors to the T-cell lineage is a crucial requirement for T-cell development, yet the timing and developmental cues regulating this process remain controversial. Here we have devised a technique to analyze the T-cell/B-cell lineage potential of precursors that have been recruited to the fetal mouse thymus but which have yet to contact the thymic epithelial microenvironment. We show that lymphoid progenitors arriving at the thymus are not bipotent T/B precursors, and provide evidence that intrathymic Notch signaling is not the mechanism determining T/B lineage choice in migrant precursors. Rather, we provide evidence that Notch signaling influences T/B lineage choice in lymphoid precursors through interactions with defined stromal components within the fetal liver. Collectively, our data redefine our understanding of the role and timing of Notch signaling in relation to lineage choices in lymphoid precursors.