Molecules controlling hematopoietic development in vertebrates

Hematopoiesis first emerges in the embryo in the extra-embryonic mesoderm i n the yolk sac, and generates primitive erythoblasts. Definitive hematopoie sis then takes place in the fetal liver and bone marrow probably after the seeding of stem cells migrating from the para-aortic region. The analysis o f the phenotype of mutant mice created by homologous recombination in ES ce lls has led to the identification of mastegenes controlling hematopoietic d evelopment. These encode two types of molecules, growth factors and transcr iption factors. Each appears to act at a very timely defined stage of stem cell development, either to specify the transition from the mesoderm to the hematopoietic differenciation, or the choice between the lymphoid or myelo id pathway, or to trigger the proliferation of defined progenitors. A hiera rchy in the activity of these genes has been proposed based on results of k nock-out experiments: in the absence of some of these molecules, hematopoie sis completely fails to occur, whereas the lack of others only compromises the development of one pathway. The ongoing challenge is now to unravel the downstream signalling pathways used by these growth and transcription fact ors to influence hematopoietic stem cell decisions.