tin

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..The properties of the how gene described herein suggest that this gene participates in the control of expression of as yet unidentified target mRNAs coding for proteins essential to cardiac and muscular activity...

..Its temporal and spatial expression patterns suggest that D-mef2 may play an important role in commitment of mesoderm to myogenic lineages...

..These events result in a diversification of heart cell identities within each segment...

..This developmental requirement of wg for cardiac organogenesis is distinct from its function in segmentation and neurogenesis. We conclude that wg signaling is a crucial component of heart formation...

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..These results define the only known in vivo target for transcriptional activation by Tinman and demonstrate that D-mef2 lies directly downstream of tinman in the genetic cascade controlling heart formation in Drosophila...

..Together, these observations suggest that Bagpipe and Biniou serve as direct, partially redundant, and tissue-specific activators of the terminal differentiation gene beta 3Tub60D in the visceral mesoderm...

..We conclude that the mesoderm is segmented in some way not dependent on the distribution of Wingless, suggesting a more permissive and less instructive role for the protein in this instance...

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..Here, we describe two homeo box genes, tinman (tin) and bagpipe (bap), which spatially subdivide the mesoderm and determine cell fates in the dorsal mesoderm...

..In many aspects the expression pattern of Drosophila hand resembles the patterns of its vertebrates orthologues, for instance in cardiac tissues. We assume that Hand proteins might play a highly conserved role throughout evolution...

..Dpp signals are required in cooperation with the mesoderm-specific NK homeodomain transcription factor Tinman (Tin) to induce all dorsal mesodermal tissue derivatives, which include dorsal somatic muscles, the dorsal vessel and ..

..These studies indicate that the primary function of laminin is to provide structural support for the various cell types, thereby enabling their proper organization into the various organs...

..Our results illustrate the utility of Drosophila as a model system to study dilated cardiomyopathy and other muscular-dystrophy-associated phenotypes...

..This demonstrates that the spatial expression of dpp in the ectoderm determines which cells of the mesoderm become competent to develop into visceral mesoderm and the heart...

..These results, together with the observed lethality of vimar mutations, indicate that vimar is one of the bagpipe target genes that are required for normal development and differentiation of the midgut visceral mesoderm...

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..It is likely that some of these functional and regulatory properties of tinman are shared by tinman-related genes from vertebrates that have similarly important roles in embryonic heart development...

..Here we show, by expressing dpp ectopically in the ectoderm and mesoderm and by examining dpp null mutant embryos, that dpp regulates expression of mesodermal genes...

..Our data presented herein suggest that Kuzbanian acts during lateral inhibition within the cardiac primordium. Furthermore we discuss a second function of Kuzbanian in heart cell morphogenesis...

..In particular, overexpression of dsh can restore heart formation in the absence of wg function. We discuss the possibility that Wg signaling is part of a combinatorial mechanism to specify the cardiac mesoderm...

..These studies establish that Htl signaling provides a vital connection between initial formation of the embryonic mesoderm in Drosophila and subsequent cell-fate specification within this germ layer...

..In support, we find that manipulation of pannier activity in either germ layer affects cardiac specification, suggesting that its function is required in both the mesoderm and the ectoderm...

..These findings suggest that salivary tube dimensions may be an intrinsic property of salivary gland cells...

..But disruption of ACER, a Drosophila ACE2 homologue, results in a severe defect of heart morphogenesis. These genetic data for ACE2 show that it is an essential regulator of heart function in vivo...

..The integration of Pointed with the combinatorial effects of dTCF, Mad, Twist, and Tinman determines inductive Ras signaling specificity in muscle and heart development...

..We also propose that in wg-expressing ectodermal cells, slp is an integral component in an autocrine feedback loop of Wg signaling...

..These findings for the first time demonstrate a specific involvement for Hox genes in patterning the muscular circulatory system, and suggest a mechanism of broad relevance for animal heart ..

..jeb reveals a signaling process in which somatic muscle precursors support the proper migration and differentiation of visceral muscle cells. Later in embryogenesis, jeb is transcribed in neurons and Jeb protein is found in axons...

The tinman (tin) and bagpipe (bap) genes are members of the NK homeobox gene family of Drosophila, so that tin occupies a higher position than bap in the regulatory hierarchy...

..In addition, the GATA factor gene pannier (pnr) and the homeobox gene tinman (tin), which are controlled by the convergence of Decapentaplegic (Dpp), fibroblast growth factor (FGF), Wingless (Wg) ..

..This indicates that wing hearts are required for proper wing morphogenesis and functionality...

..At stage 10, the mesodermal expression patterns of D-six4 and tin are complementary, being restricted to the dorsal and non-dorsal regions respectively...

..Conservation of phyletic body plans may have been due to the retention since pre-Cambrian time of GRN kernels, which underlie development of major body parts...

..Thus, the spatial precision of cell type specification within an organ depends on multiple phases of inductive interaction between the ectoderm and the mesoderm...

..Embryonic PCs belong to three distinct genetic classes based on Odd-skipped (Odd), Even-skipped (Eve) and Tinman (Tin) expression...

..The lSHM contributes hemocytes, as well as the nephrocytes forming the subesophageal body, also called garland cells...

..In Drosophila, the Hox segmentation gene abdominal-A (abd-A) is required for the specification of a functionally distinct heart region at ..

..Such findings implicate Toll as a critical cell adhesion molecule in the alignment and migration of cardioblasts during dorsal vessel morphogenesis...

During germ-band extension, Decapentaplegic (Dpp) signals from the dorsal ectoderm to maintain Tinman (Tin) expression in the underlying mesoderm. This signal specifies the cardiac field, and homologous genes (BMP2/4 and Nkx2...

..Mutational analysis in mice and, as particular focus of this review, in zebrafish, reveals the additional genes brought into play to fashion these evolutionarily 'new' organotypic components...

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..Thus, integration of positive and negative regulators on enhancers of target genes appears to be an important mechanism in tissue-specific induction by TGF-beta molecules...

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..These cardiac defects may be the cause of death of these mutants during late embryonic or early larval stages...

..This signalling crosstalk might explain the complexity of the responses to TGF-beta and related factors...

..These novel genes show a variety of expression patterns and also differ in their dependence on twist and snail functions. This indicates that the regulation of early gene activity in the mesoderm is more complex than previously thought...

NK-4, also called msh2 and tinman, encodes a homeodomain transcription factor that is required for the development of the dorsal mesoderm and its derivatives in the Drosophila embryo...

..The related GATA4 protein of mice likewise functions as a cardiogenic factor in Drosophila, demonstrating an evolutionarily conserved function between Pannier and GATA4 in heart development...

..In this paper, we discuss molecular mechanisms of cardiovascular development with particular emphasis on roles of transcription factors...

..pathway act downstream of Htl, and 3) establish a functional relationship between the Ras pathway and Tinman (Tin), a homeodomain factor that is essential for specifying some of the same dorsal mesodermal cells that are dependent ..

..The combinatorial expression of SRF, a MADS box factor Nkx2-5 (a NK4 homeodomain), and/or GATA4, a dual C4 zinc finger protein, in heterologous CV1 fibroblasts and Schneider 2 insect ..

..Taken together, these results demonstrate a critical role for the Ush transcriptional regulator in several diverse processes of mesoderm differentiation and heart formation...

..Recent studies have shown that the BMP signal transduction cascade can be modulated at every step of this process...

..Signaling pathways that establish the tin expression domain also appear to be conserved in vertebrates...

..The observation of a few QTL with moderate to large effects will facilitate positional cloning of genes underlying sexual isolation...

..We show that an extracellular matrix component is specifically expressed at the surface of the dorsal vessel and could participate in the interaction between the dorsalmost ectodermal cells and the heart during this migration step...

..Other miRNAs might promote specific developmental switches during the development and regeneration of muscles...

..Our results support the hypothesis that the exit glia have a mesodermal origin and that glia play an essential role in determining transverse nerve axon pathways...

..Our findings suggest that muscle determination in Drosophila is regulated by induction between germ layers during gastrulation...

..Genetic interactions and the strikingly similar phenotypes of mutations in shn and the dpp receptors encoded by thick veins and punt suggest that shn plays a downstream role in dpp signaling...

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In the Drosophila larval cardiac tube, aorta and heart differentiation are controlled by the Hox genes Ultrabithorax (Ubx) and abdominal A (abdA), respectively...

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..Finally, I have mapped an enhancer trap element within the 5' region of dFKBP59 which may help in future studies to address the question of its function during Drosophila development...

..Thus the vm1 enhancer of the beta3 tubulin gene contains a complex array of elements that are involved in transactivation by a combination of tissue- and position-specific factors including Tinman and UBX...

..In combination with the axial information furnished by abd-A, the segmental hh-dependent information leads to the differentiation of the six pairs of svp-expressing cells into functional ostiae...

..The core of this enhancer contains two evolutionarily conserved binding sites for the homeodomain protein Tinman (Tin), expressed in developing cardiac, somatic, and visceral muscle lineages...

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..In Drosophila, the NK-2 class homeobox gene tinman (tin) is expressed in cardiac and visceral mesodermal progenitors and is essential for their specification...

..Recent work in Drosophila has built a picture of the gene activities that specify the gonad and allow it to attract germ cells, and has led to the identification of a gene, columbus, that may encode the attractive factor...

..The integration of this new information with previous findings has allowed us to draw a more complete pathway of regulatory events during cardiac induction and differentiation in Drosophila...

..the reduction of Zfh1 positive cell types, thereby restricting the number of Odd-skipped (Odd) positive and Tinman (Tin) positive pericardial cells in the dorsal mesoderm...

..And we present the bioinformatics tools and databases of genomic sequence collections to the experimentalist. All of the individual goals detailed above are direct responses to this view. ..

..And we present the bioinformatics tools and databases of genomic sequence collections to the experimentalist. All of the individual goals detailed above are direct responses to this view. ..

..Analysis of the phenotype of Ptn/Mk mutants in Drosophila will clarify the signaling function of these molecules both with respect to the pathways in which they participate and their functions in those pathways. ..

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..Numerous letters from outside investigators attesting interest in this facility are included as an Appendix to this application. ..

..The combination of cellular, molecular and genetic studies proposed in this project will provide new and in-depth insight into mechanisms of primitive heart tube morphogenesis. ..

..And we present the bioinformatics tools and databases of genomic sequence collections to the experimentalist. All of the individual goals detailed above are direct responses to this view. ..

..Mutations identified from this screen will provide entry points to dissect genetic and molecular pathways involved in vertebrate organogenesis. ..

..Our practice must get beyond struggling to ameliorate effects rather than altering causes. This research shows the way to discovery of structure and function in causal genomic control systems. ..

..PUBLIC HEALTH RELEVANCE: Protein signals move between cells to coordinate decisions. We study how these signals make cells do the right thing at the right time. ..

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..The studies in this proposal will help elucidate cellular and molecular mechanisms underlying cardiac fibrillation and ultimately contribute to the development of new preventive and therapeutic approaches. ..

..And we present the bioinformatics tools and databases of genomic sequence collections to the experimentalist. All of the individual goals detailed above are direct responses to this view. ..

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..The combination of cellular, molecular and genetic studies proposed in this project will provide new and in-depth insight into mechanisms of primitive heart tube morphogenesis. ..

..PUBLIC HEALTH RELEVANCE: Protein signals move between cells to coordinate decisions. We study how these signals make cells do the right thing at the right time. ..

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..Some of the principles arising from studies in the muscle system may also be applicable to other developmental systems, and thus will potentially contribute to our understanding of other developmental defects in humans. ..

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..In addition, the investigators need to carry out several unique computational analyses that reflect the particular features of the S. purpuratus genome. ..

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..Through this proposed work, we wish to furnish the field with a better understanding of the role of the TGFb/Smad pathway in physiology and a better ability to manage this pathway in tumor progression, metastasis and other disorders. ..