ANTIGENIC PHENOTYPE AND GENE-EXPRESSION PATTERN OF LYMPHOHEMATOPOIETIC PROGENITORS DURING EARLY MOUSE ONTOGENY

Hemopoiesis, initiated in the early embryo yolk sac (YS) (7.5-8 days p ostcoitum (pc) in mouse), takes place thereafter in sites successively seeded by extrinsic hemopoietic stem cells (HSC). Since the existence of intraembryonic HSC has been proven experimentally in some vertebra tes, it is also likely that not all HSC originate in the YS in mammals , as previously thought. Candidate intraembryonic sites that may be ac tive in producing HSC before liver colonization are the para-aortic sp lanchnopleura (P-Sp) and the aorta-gonads-mesonephros region (AGM). He re we explore these sites directly for the presence of cells with hemo poietic-specific surface molecules and gene activities. The Ags c-kit, AA4.1, Mac-1, and Sca-1 begin to be expressed on some P-Sp and ACM ce lls, making it possible to distinguish subpopulations that evolve acco rding to reproducible developmental patterns. On the basis of RAG-1 ge ne transcription, the first lymphoid precursors in the mouse embryo ap pear to be present 9.5 to 10 days pc in P-Sp/AGM and YS. Starting B-ce ll lymphopoiesis (9-12 days pc) is characterized by nonexpression of t he surrogate light chain lambda 5-encoding gene and biased usage of Ig H DJ4 rearrangements. In the 12.5- to 13.5-day-pc fetal liver (FL), a switch occurs, characterized by the random use of all IgH DJ and the d etection of lambda 5 gene transcripts.