In many instances during development, morphogens specify cell fates by forming concentration gradients. In the Drosophila melanogaster wing imaginal disc, Decapentaplegic (Dpp), a bone morphogenetic protein (BMP), functions as a long-range morphogen to control patterning and growth. Dpp is secreted from a stripe of cells at the anterior-posterior compartment boundary and spreads into both compartments to generate a characteristic BMP activity gradient. Ever since the identification of the morphogen activity of Dpp in the developing wing, the system has served as a paradigm to understand how long-range gradients are established and how cells respond to such gradients. Here we reveal the tight and direct connection of these two processes with the identification and characterization of pentagone (pent), a transcriptional target of BMP signalling encoding a secreted regulator of the pathway. Absence of pent in the wing disc causes a severe contraction of the BMP activity gradient resulting in patterning and growth defects. We show that Pent interacts with the glypican Dally to control Dpp distribution and provide evidence that proper establishment of the BMP morphogen gradient requires the inbuilt feedback loop embodied by Pent.

Blood and endothelial cells arise in close association in developing embryos, possibly from a shared precursor, the hemangioblast, or as hemogenic endothelium. The transcription factor, Scl/Tal1 (stem cell leukemia protein), is essential for hematopoiesis but thought to be required only for remodeling of endothelium in mouse embryos. By contrast, it has been implicated in hemangioblast formation in embryoid bodies. To resolve the role of scl in endothelial development, we knocked down its synthesis in zebrafish embryos where early precursors and later phenotypes can be more easily monitored. With respect to blood, the zebrafish morphants phenocopied the mouse knockout and positioned scl in the genetic hierarchy. Importantly, endothelial development was also clearly disrupted. IntroductionDuring mammalian and avian embryogenesis, hematopoietic precursors arise in close association with the vasculature in the blood islands of the extra-embryonic yolk sac (YS) and in the ventral wall of the dorsal aorta (DA), in the aorta-gonads-mesonephros (AGM) region. These observations have led to the hypothesis that the 2 cell types arise from a common precursor, the hemangioblast. Coexpression of blood and endothelial genes, and the dependence of both lineages on several of them, are cited as evidence (for a review, see Keller 1 ). In addition, single cells expressing the vascular endothelial growth factor (VEGF) receptor, flk1, isolated from embryoid bodies (EBs), differentiate in vitro into blast colonies, consisting of both hematopoietic and endothelial progenitors. These blast colonyforming cells (BL-CFCs) therefore represent the in vitro equivalent of the hemangioblast. 2 However, the definitive lineage-labeling experiment to prove the in vivo existence of the hemangioblast has yet to be performed.The concept of hemogenic endothelium has also acquired significant experimental support over recent years. Label targeted to endothelial cells (ECs) has been found later in the emerging clusters of cells containing the first hematopoietic stem cells (HSCs) in the DA (Jaffredo et al 3 and references therein). Consistent with these data, purified ECs from both mouse and human embryos have been shown to possess hematopoietic potential. [4][5][6] Taken together, the hemangioblast and hemogenic endothelium data strongly link hematopoiesis with at least a subset of EC development.One gene, expressed in hemangioblast populations, is scl/tal1, hereafter referred to as scl. The gene encodes a basic helix-loophelix (bHLH) transcription factor, which was initially discovered at the sites of chromosomal translocations in leukemic T cells (for a review, see Begley and Green 7 ). Gene ablation studies in the mouse have revealed an essential role for scl in hematopoiesis. Scl Ϫ/Ϫ mouse embryos die at embryonic day 9.5 (E9.5) due to a complete absence of primitive blood cells. 8,9 Subsequent studies in chimeras revealed that scl Ϫ/Ϫ ES cells were also unable to contribute to definitive hematopoiesis. 10,11 Using conditional knockouts, scl req...