The biological effects of endogenous bone morphogenetic protein 4 (BMP-4), a member of the transforming growth factor 13 family, on embryonic development of Xenopus laevis were investigated by using a functionally defective mutant of the BMP-4 receptor (AmTFR11)
Vertebrate embryonic blood formation is regulated by factors that participate in dorsal-ventral patterning and mesoderm induction. The GATA-binding transcription factors are required for normal hematopoiesis and are expressed during gastrulation when ventral mesoderm (VM) is induced to form blood. Based on the recent demonstration that bone morphogenetic protein (BMP-4) is a potent ventralizing factor and inducer of hematopoietic tissue, we hypothesized that GATA-2 could be induced or activated by BMP-4. Here we demonstrate that BMP-4 can stimulate GATA-2 expression, and that expression of a dominant negative BMP-4 receptor can suppress GATA-2 induction by BMP-4 in ventral mesoderm. Over-expression of GATA-2 in ventral mesoderm leads to increased globin production and forced expression of GATA-2 in primitive ectoderm adjacent to ventral mesoderm also stimulates globin expression. Our results suggest that BMP-4 and GATA-2 can function in two adjacent germ layers, mesoderm and ectoderm, to participate in blood cell formation during embryogenesis.
A recent study revealed the presence of a unique population of myeloid cells in the anterior ventral (AV) mesoderm of Xenopus laevis embryo, as characterized by the expression of peroxidase 2 (POX2), which encodes for a leukocyte-specific enzyme. The current report further characterized the POX2-positive cells in terms of their contribution to hematopoiesis in tadpole and regulatory mechanism in differentiation. Grafting experiments with cytogenetically labeled tissues revealed that AV-derived mesoderm supplies a transient population of migrating leukocytes in the mesenchyme of early tadpole. These cells were rarely found in blood vessels at any stages. Using a ventral marginal zone explant system, we demonstrated that dkk1, shown as a heart inducer in this system, has a strong ability to induce the expression of POX2. Injection of a high dose dkk1 RNA induced a heart marker while a low dose of dkk1 preferentially induced the expression of POX2, suggesting that dkk1 works as a morphogen to determine the different lineages. Overall results indicate that wnt signal inhibitors induce leukocytes at the early neurula stage and that these cells spread to the entire body and exist until the ventral blood island-derived leukocytes appear in the body.
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