Flk-1 expression defines a population of early embryonic hematopoietic precursors.

We have investigated the expression pattern of the Flk-1 receptor tyrosine kinase in mouse embryonic and fetal hematopoietic tissues as well as on hematopoietic precursor cells derived from these tissues. RNA analysis indicated that flk-1 was expressed in the yolk sac at day 10 of gestation, in the whole embryo at day 10 and 12 of gestation, in the liver throughout fetal life and in embryoid bodies (EBs) generated from ES cells differentiated in culture. Flk-1 message was also detected in erythroid and macrophage colonies generated from precursors of yolk sac, fetal liver, adult marrow and EB origin.

A common precursor for primitive erythropoiesis and definitive haematopoiesis.

The generation of blood cells, haematopoiesis, in the mouse embryo begins with the development of primitive nucleated erythroid cells in the yolk sac followed by the appearance of precursors for multiple definitive haematopoietic lineages. The later developing lineages arise from multipotential stem cells, but the relationship of primitive erythroid cells to these other haematopoietic populations is unknown. Using an in vitro embryonic stem (ES) cell differentiation system, we show that primitive erythrocytes and other haematopoietic lineages arise from a common multipotential precursor that develops within embryoid bodies generated from differentiated ES cells.

The role of the carboxy terminus of v-Rel in transformation and activation of endogenous gene expression.

Proteins within the Rel/NF-kappa B transcription factor family can be divided into two functional domains, a homologous amino terminal region, the Rel Homology Domain, and a divergent carboxy terminal domain. The amino terminal sequences specify DNA binding, nuclear localization, and interaction with the I kappa B family of inhibitory proteins. The carboxy terminus of each protein functions as a transcriptional activation domain, however, precise definition of sequence requirements has been difficult.

The Rel family of proteins in oncogenesis and differentiation.

The Rel family consists of a large set of related proteins containing a conserved protein region, termed the Rel Homology Domain. Although the prototype member of the Rel family, v-Rel, was originally discovered on the basis of its transforming ability, recent studies have indicated that other members are also important mediators of embryonic development and differentiation. In particular, the dorsal protein is an essential embryonic polarity gene required for the proper dorsal/ventral development of the Drosophila embryo, while the avian c-rel gene has been implicated in the control of cell death and tissue molding.

High levels of c-rel expression are associated with programmed cell death in the developing avian embryo and in bone marrow cells in vitro.

To determine the physiological processes in which the transcription factor c-Rel may act, we have examined its pattern of expression in the avian embryo by in situ hybridization. These studies showed that c-rel is expressed ubiquitously at low levels and at high levels in isolated cells undergoing programmed cell death by apoptosis or autophagocytosis. To further establish a functional link between expression of c-rel and cell death, we examined the biological consequences of c-rel overexpression in vitro.