From the hemangioblast to self-tolerance: a series of innovations gained from studies on the avian embryo

During the last decades of the 20th century, studies on the vertebrate hematopoietic and immune systems have largely been performed, on mammalian models. The mouse has been the preferred material for several cogent reasons: (i) numerous well defined genetic strains are available; (ii) this species has been and still is instrumental in the study of gene activity through transgenesis; and (iii) in vitro culture techniques and in vivo assays for blood cells together with a wide array of antibodies and nucleic acid probes have been developed to investigate the cellular interactions occurring during hematopoiesis and immune reactivity. However, important and fundamental notions have emerged from using another higher vertebrate model, the avian embryo. The distinction among small lymphocytes of two populations, the T and B lymphocytes, endowed with different roles in adaptive immunity and dependant on different environments for their specification, has relied on experiments carried out in birds. The avian model has been critical for the analysis of the origin and traffic of hematopoietic precursor cells. It allowed the demonstration that both hematopoietic and angioblastic lineages arise from a common precursor, a cell whose existence had been proposed but never undoubtedly proven, the hemangioblast. Finally a form of thymus-dependant 'dominant' tolerance was demonstrated on the basis of experiments in the avian embryo, which initiated a large current of studies on 'regulatory T-cells'. Work in this model during the last decades has relied strongly on the construction of chimeras between quail and chick embryos that allowed a refined analysis of cell behaviour during embryogenesis. The novel perception of developmental neuropoiesis and immunopoiesis that followed proved to be largely applicable to lower and higher vertebrates, notably mammals.