Transcription factor GATA-3 is required for development of the T-cell lineage.
THE zinc-finger transcription factor GATA-3 is expressed in haematopoietic cells and in the developing kidney and nervous system. Within the haematopoietic lineages, expression of GATA-3 is restricted to thymocytes and T cells. Functionally important GATA-3 binding sites have been identified in multiple T-cell-specific genes. Mice containing homozygous null mutations of the GATA-3 gene die on embryonic day 12, precluding a detailed assessment of the role of GATA-3 in haematopoietic development. Here we have used murine embryonic stem (ES) cells containing homozygous mutations in the GATA-3 gene (GATA-3(-/-)) in conjunction with the RAG-2(-/-) (ref. 10) and C57BL/6 complementation systems to study the role of GATA-3 in mammalian haematopoiesis. Our results show that GATA-3(-/-) ES cells can contribute to the development of the mature erythroid, myelomonocytic and B-cell lineages, but fail to give rise to thymocytes or mature peripheral T cells. The differentiation of GATA-3(-/-) T cells is blocked at or before the earliest double-negative (CD4-/CD8-) stage of thymocyte development, such that the GATA-3(-/-) ES cells are unable to contribute measurably to the double-negative thymocyte population. These findings suggest that GATA-3 is an essential and specific regulator of early thymocyte development.
Ting
C N
CN
The Departments of Medicine and Pathology, University of Chicago, Illinois 60637, USA.
Olson
M C
MC
Barton
K P
KP
Leiden
J M
JM
D000818:Animals; D001755:Blastocyst; D001854:Bone Marrow Cells; D002454:Cell Differentiation / Q000235:genetics / Q000502:physiology; D002460:Cell Line; D019070:Cell Lineage; D002678:Chimera; D004268:DNA-Binding Proteins / Q000235:genetics / Q000502:physiology*; D005434:Flow Cytometry; D050990:GATA3 Transcription Factor; D006410:Hematopoiesis / Q000235:genetics / Q000502:physiology*; D051379:Mice; D008810:Mice, Inbred C57BL; D011506:Proteins / Q000235:genetics; D017384:Sequence Deletion; D013154:Spleen / Q000166:cytology; D013601:T-Lymphocytes / Q000166:cytology*; D013950:Thymus Gland / Q000166:cytology; D015534:Trans-Activators / Q000235:genetics / Q000502:physiology*; D016335:Zinc Fingers
D004268:DNA-Binding Proteins; D050990:GATA3 Transcription Factor; C494748:Gata3 protein, mouse; D011506:Proteins; C499308:Rag2 protein, mouse; D015534:Trans-Activators; C064655:V(D)J recombination activating protein 2