T/B lineage choice occurs prior to intrathymic Notch signaling.
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.
Harman
Benjamin C
BC
Dept of Anatomy, Institute for Biomedical Research, University of Birmingham, Edgbaston, Birmingham, B15 2TT, United Kingdom.
Jenkinson
William E
WE
Parnell
Sonia M
SM
Rossi
Simona W
SW
Jenkinson
Eric J
EJ
Anderson
Graham
G
D000818:Animals; D001402:B-Lymphocytes / Q000166:cytology / Q000502:physiology*; D002450:Cell Communication; D019070:Cell Lineage; D018920:Coculture Techniques; D004847:Epithelial Cells / Q000166:cytology / Q000502:physiology; D005333:Fetus; D008099:Liver / Q000166:cytology / Q000196:embryology; D008565:Membrane Proteins / Q000502:physiology*; D051379:Mice; D008807:Mice, Inbred BALB C; D018345:Mice, Knockout; D000072183:Phosphatidylinositol-3,4,5-Trisphosphate 5-Phosphatases; D010744:Phosphoric Monoester Hydrolases / Q000172:deficiency / Q000235:genetics; D051880:Receptors, Notch; D017154:Stromal Cells / Q000166:cytology / Q000502:physiology; D013601:T-Lymphocytes / Q000166:cytology / Q000502:physiology*; D013950:Thymus Gland / Q000166:cytology*
D008565:Membrane Proteins; D051880:Receptors, Notch; D010744:Phosphoric Monoester Hydrolases; C098706:INPPL1 protein, human; D000072183:Phosphatidylinositol-3,4,5-Trisphosphate 5-Phosphatases