Hand is a direct target of Tinman and GATA factors during Drosophila cardiogenesis and hematopoiesis

Department of Molecular Biology, University of Texas Southwestern Medical Center at Dallas, 6000 Harry Hines Boulevard, Dallas, TX 75390, USA.
Development (Impact Factor: 6.27). 09/2005; 132(15):3525-36. DOI: 10.1242/dev.01899
Source: PubMed

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.

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    • "Thus, severely compromised integrin/ ILK pathway function is detrimental for the heart, but fine-tuned moderate reduction maintains youthful cardiac performance, suggesting a dual role for this complex in regulating cardiac integrity and aging. Results ilk heterozygous mutants have extended lifespan in Drosophila As the RNAi-mediated KD of ilk extends lifespan in C. elegans (Hansen et al., 2005; Curran & Ruvkun, 2007; Kumsta et al., 2014), we wondered whether reduced ilk expression is also beneficial to longevity in Drosophila. As lifespan can be significantly modulated by genetic background (Grandison et al., 2009), we first backcrossed ilk 54 mutants (premature stop codon; Zervas et al., 2011 "
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    Aging cell 01/2014; 13(3). DOI:10.1111/acel.12193 · 5.94 Impact Factor
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    • "Similar Figure 2. jumu and CHES-1-like Embryonic Expression and Loss-of-Function Cardiac Phenotypes (A and B) jumu (A) and CHES-1-like (B) mRNAs are expressed in the cardiac mesoderm at embryonic stage 11 (arrows). (C–E) Whole embryo RNAi results for dsRNA corresponding to lacZ (C), jumu (D), and CHES-1-like (E) in live embryos in which CCs express a nuclear localized form of GFP under control of a Hand enhancer (Han and Olson, 2005), and PCs express both Hand-GFP nuc and a nuclear form of DsRed under control of a heart enhancer from the Him gene (Him-DsRED nuc ; A.M.M. and S. Michaud, unpublished data). Arrows indicate incorrect numbers and uneven distribution of CCs and PCs. "
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    Developmental Cell 07/2012; 23(1):97-111. DOI:10.1016/j.devcel.2012.05.011 · 10.37 Impact Factor
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    • "12 and UAS-jumu (Strodicke et al., 2000; Hofmann et al., 2009); TinD-GAL4 (Yin et al., 1997); twi-GAL4 (Greig and Akam, 1993); and Hand-GAL4 (Han and Olson, 2005). Mutant chromosomes were maintained over the TM3, ftz-lacZ balancer. "
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    ABSTRACT: A common theme in developmental biology is the repeated use of the same gene in diverse spatial and temporal domains, a process that generally involves transcriptional regulation mediated by multiple separate enhancers, each with its own arrangement of transcription factor (TF)-binding sites and associated activities. Here, by contrast, we show that the expression of the Drosophila Nidogen (Ndg) gene at different embryonic stages and in four mesodermal cell types is governed by the binding of multiple cell-specific Forkhead (Fkh) TFs - including Biniou (Bin), Checkpoint suppressor homologue (CHES-1-like) and Jumeau (Jumu) - to three functionally distinguishable Fkh-binding sites in the same enhancer. Whereas Bin activates the Ndg enhancer in the late visceral musculature, CHES-1-like cooperates with Jumu to repress this enhancer in the heart. CHES-1-like also represses the Ndg enhancer in a subset of somatic myoblasts prior to their fusion to form multinucleated myotubes. Moreover, different combinations of Fkh sites, corresponding to two different sequence specificities, mediate the particular functions of each TF. A genome-wide scan for the occurrence of both classes of Fkh domain recognition sites in association with binding sites for known cardiac TFs showed an enrichment of combinations containing the two Fkh motifs in putative enhancers found within the noncoding regions of genes having heart expression. Collectively, our results establish that different cell-specific members of a TF family regulate the activity of a single enhancer in distinct spatiotemporal domains, and demonstrate how individual binding motifs for a TF class can differentially influence gene expression.
    Development 02/2012; 139(8):1457-66. DOI:10.1242/dev.069005 · 6.27 Impact Factor
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