Hand is a direct target of Tinman and GATA factors during Drosophila cardiogenesis and hematopoiesis
ABSTRACT The existence of hemangioblasts, which serve as common progenitors for hematopoietic cells and cardioblasts, has suggested a molecular link between cardiogenesis and hematopoiesis in Drosophila. However, the molecular mediators that might link hematopoiesis and cardiogenesis remain unknown. Here, we show that the highly conserved basic helix-loop-helix (bHLH) transcription factor Hand is expressed in cardioblasts, pericardial nephrocytes and hematopoietic progenitors. The homeodomain protein Tinman and the GATA factors Pannier and Serpent directly activate Hand in these cell types through a minimal enhancer, which is necessary and sufficient to drive Hand expression in these different cell types. Hand is activated by Tinman and Pannier in cardioblasts and pericardial nephrocytes, and by Serpent in hematopoietic progenitors in the lymph gland. These findings place Hand at a nexus of the transcriptional networks that govern cardiogenesis and hematopoiesis, and indicate that the transcriptional pathways involved in development of the cardiovascular, excretory and hematopoietic systems may be more closely related than previously appreciated.
SourceAvailable from: Bama Charan Mondal[Show abstract] [Hide abstract]
ABSTRACT: eLife digest Progenitor cells are cells that can either multiply to make new copies of themselves or mature into different specialized cell types—such as blood cells. In the fruit fly Drosophila, new blood cells are formed in several different locations, including in an organ called the lymph gland. In 2011, researchers found that the fate of blood progenitor cells within the lymph gland is controlled by signals from two nearby sources—one from specialized, supportive (‘niche’) cells and the other from maturing blood cells. The signal from the maturing blood cells ensures that the relative amounts of progenitor and maturing blood cells are kept in the right balance. As a result, this signaling process has been called ‘equilibrium signaling’. Questions remain as to how equilibrium signaling is regulated, and how it interacts with signals from the niche. To investigate this, Mondal et al.—including some of the researchers involved in the 2011 work—used various genetic techniques to create Drosophila larvae in which the tissues that become blood cells are made visible with fluorescent proteins. This meant that these tissues could be examined in live, whole animals by using a microscope. Mondal et al. then searched for the Drosophila genes involved in generating new blood cells in the lymph gland—particularly those involved in equilibrium signaling. This was done by switching on and off hundreds of genes, one by one, in the lymph gland, and any genes that caused changes to the generation of new blood cells were then investigated further. Following these investigations, Mondal et al. focused on three genes—and when each of these genes was switched off in maturing blood cells, the result was that fewer progenitor cells remained in the lymph gland. This effect was not seen when the genes were switched off in the progenitor or the niche cells, which suggested that the genes are likely to be components of the equilibrium signaling pathway. Switching off these genes in maturing blood cells also dramatically reduced the levels of a protein called Pvr, a key equilibrium signaling protein known from the 2011 study and an important player in blood cell development in several species. How the newly identified genes actually control Pvr protein levels to maintain proper equilibrium signaling in the lymph gland remains to be explored. However, this work provides a basis for investigating the role of related genes in blood cell development in vertebrate systems, namely humans. DOI: http://dx.doi.org/10.7554/eLife.03626.002eLife Sciences 09/2014; 3:e03626. DOI:10.7554/eLife.03626 · 8.52 Impact Factor
03/2015; 2(1):2-16. DOI:10.3390/jcdd2010002
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ABSTRACT: The Drosophila heart is a linear organ formed by the movement of bilaterally specified progenitor cells to the midline and adherence of contralateral heart cells. This movement occurs through the attachment of heart cells to the overlying ectoderm which is undergoing dorsal closure. Therefore heart cells are thought to move to the midline passively. Through live imaging experiments and analysis of mutants that affect the speed of dorsal closure we show that heart cells in Drosophila are autonomously migratory and part of their movement to the midline is independent of the ectoderm. This means that heart formation in flies is more similar to that in vertebrates than previously thought. We also show that defects in dorsal closure can result in failure of the amnioserosa to properly degenerate, which can physically hinder joining of contralateral heart cells leading to a broken heart phenotype.Developmental Biology 09/2014; 396(2). DOI:10.1016/j.ydbio.2014.08.033 · 3.64 Impact Factor