Abstract

The focus of the proposed research is to elucidate the molecular-genetic mechanisms that are responsible for specifying the mesodermal progenitor cells that will give rise to heart. It has been shown that the functions of the homeobox gene, tinman, and the secreted factors wingless (wg) and hedgehog (hh) are required for the formation of the heart progenitor cells, indicating a critical role in mesodermal patterning.
The aim i s to understand how tinman and the wg/hh signals determine the formation and developmental fate of the cardiac mesoderm.
The specific aims are: 1) To define the requirements for the tinman gene in heart formation: a) to understand the precise temporal and spatial requirements of tinman by using specific promoters to drive tinman expression in transgenic flies and by generating mosaic flies of wild-type and mutant tissue; to test whether vertebrate and fly heart development is similar by expressing tinman-related genes from various vertebrate species in tinman mutant flies and examining their ability to restore heart development. 2) To understand the regulation of tinman expression in the heart by expressing wg/hh in the mutant background of the other and by generating genetic mosaics. The tinman promoter will be dissected in vivo to identify heart-specific elements and to isolate new transcriptional regulators that bind to heart- specific enhancers of the tinman gene.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Research Project (R01)
Project #
5R01HL054732-03
Application #
2460137
Study Section
Cardiovascular and Pulmonary Research A Study Section (CVA)
Project Start
1995-08-01
Project End
1999-07-31
Budget Start
1997-08-01
Budget End
1998-07-31
Support Year
3
Fiscal Year
1997
Total Cost
Indirect Cost

  Institution

Name
University of Michigan Ann Arbor
Department
Biology
Type
Schools of Arts and Sciences
DUNS #
791277940
City
Ann Arbor
State
MI
Country
United States
Zip Code
48109

  Publications

Blice-Baum, Anna C; Guida, Maria Clara; Hartley, Paul S et al. (2018) As time flies by: Investigating cardiac aging in the short-lived Drosophila model. Biochim Biophys Acta Mol Basis Dis :
Walls, Stanley M; Cammarato, Anthony; Chatfield, Dale A et al. (2018) Ceramide-Protein Interactions Modulate Ceramide-Associated Lipotoxic Cardiomyopathy. Cell Rep 22:2702-2715
Zanon, Alessandra; Kalvakuri, Sreehari; Rakovic, Aleksandar et al. (2017) SLP-2 interacts with Parkin in mitochondria and prevents mitochondrial dysfunction in Parkin-deficient human iPSC-derived neurons and Drosophila. Hum Mol Genet 26:2412-2425
Sessions, Ayla O; Kaushik, Gaurav; Parker, Sarah et al. (2017) Extracellular matrix downregulation in the Drosophila heart preserves contractile function and improves lifespan. Matrix Biol 62:15-27
Diop, Soda Balla; Birse, Ryan T; Bodmer, Rolf (2017) High Fat Diet Feeding and High Throughput Triacylglyceride Assay in Drosophila Melanogaster. J Vis Exp :
Zarndt, Rachel; Walls, Stanley M; Ocorr, Karen et al. (2017) Reduced Cardiac Calcineurin Expression Mimics Long-Term Hypoxia-Induced Heart Defects in Drosophila. Circ Cardiovasc Genet 10:
Blice-Baum, Anna C; Zambon, Alexander C; Kaushik, Gaurav et al. (2017) Modest overexpression of FOXO maintains cardiac proteostasis and ameliorates age-associated functional decline. Aging Cell 16:93-103
Gan, Zhuohui; Powell, Frank L; Zambon, Alexander C et al. (2017) Transcriptomic analysis identifies a role of PI3K-Akt signalling in the responses of skeletal muscle to acute hypoxia in vivo. J Physiol 595:5797-5813
Del Álamo, Juan C; Lemons, Derek; Serrano, Ricardo et al. (2016) High throughput physiological screening of iPSC-derived cardiomyocytes for drug development. Biochim Biophys Acta 1863:1717-27
Trujillo, Gloriana V; Nodal, Dalea H; Lovato, Candice V et al. (2016) The canonical Wingless signaling pathway is required but not sufficient for inflow tract formation in the Drosophila melanogaster heart. Dev Biol 413:16-25

Showing the most recent 10 out of 58 publications