Heart muscle is among the earliest differentiated tissues to appear in the developing embryo because a functioning heart is crucial to embryonic development and viability. We know surprisingly little, however, about how the heart forms, or about the mechanisms that regulate discrete steps along the pathway of heart muscle cell specification, proliferation and differentiation. In large part, our lack of knowledge can be traced to the absence of in vitro cell models that can recreate key aspects of heart muscle cell development. We have recently developed two in vitro culture assays that will enable us to address important questions concerning early heart development. Accordingly, the research in this proposal will use these assays to investigate how cellular interactions and growth factor signaling molecules regulate the appearance of heart muscle precursor cells in the avian embryo. One assay utilizes explants of posterior marginal zone epiblast and hypoblast from pregastrula embryos, the second uses discrete areas and cell layers within the primitive streak and Hensen's node of early gastrulae. Based upon preliminary studies, we have proposed that heart muscle precursor cells become specified in response to growth factor signals from surrounding cell layers and tissues, including the hypoblast, Hensen's node and emerging endoderm. Experiments will test this proposition by investigating the inductive interactions between responding and inducing cell layers that lead to the appearance of specified premyocardial cells, and by searching for growth factors that can induce heart muscle in responsive cell layers. Experiments will also investigate the potential role of newly formed endoderm in regulating development of heart muscle precursor cells, and will investigate how Tinman (Nkx-2,5) and MEF2 gene expression is regulated during specification of precardiac mesoderm. Results of these studies will increase our understanding of both normal and abnormal heart development and may suggest ways to alter heart development or the replication of cardiac myocytes.

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Research Project (R01)
Project #
5R01HL054133-03
Application #
2702278
Study Section
Human Embryology and Development Subcommittee 1 (HED)
Project Start
1996-05-03
Project End
1999-07-06
Budget Start
1998-05-01
Budget End
1999-07-06
Support Year
3
Fiscal Year
1998
Total Cost
Indirect Cost
Name
University of Arizona
Department
Veterinary Sciences
Type
Schools of Earth Sciences/Natur
DUNS #
City
Tucson
State
AZ
Country
United States
Zip Code
85721
Zhang, Wenjun; Yatskievych, Tatiana A; Baker, Robert K et al. (2004) Regulation of Hex gene expression and initial stages of avian hepatogenesis by Bmp and Fgf signaling. Dev Biol 268:312-26
Bell, George W; Yatskievych, Tatiana A; Antin, Parker B (2004) GEISHA, a whole-mount in situ hybridization gene expression screen in chicken embryos. Dev Dyn 229:677-87
Vokes, Steven A; Yatskievych, Tatiana A; Heimark, Ronald L et al. (2004) Hedgehog signaling is essential for endothelial tube formation during vasculogenesis. Development 131:4371-80
Baker, Robert K; Antin, Parker B (2003) Ephs and ephrins during early stages of chick embryogenesis. Dev Dyn 228:128-42
Antin, Parker B; Bales, Mark A; Zhang, Wenjun et al. (2002) Precocious expression of cardiac troponin T in early chick embryos is independent of bone morphogenetic protein signaling. Dev Dyn 225:135-41
Zhang, Wenjun; Yatskievych, Tatiana A; Cao, Xu et al. (2002) Regulation of Hex gene expression by a Smads-dependent signaling pathway. J Biol Chem 277:45435-41
Baker, R K; Vanderboom, A K; Bell, G W et al. (2001) Expression of the receptor tyrosine kinase gene EphB3 during early stages of chick embryo development. Mech Dev 104:129-32
Rudy, D E; Yatskievych, T A; Antin, P B et al. (2001) Assembly of thick, thin, and titin filaments in chick precardiac explants. Dev Dyn 221:61-71
Gregorio, C C; Antin, P B (2000) To the heart of myofibril assembly. Trends Cell Biol 10:355-62
Gerber, W V; Yatskievych, T A; Antin, P B et al. (1999) The RNA-binding protein gene, hermes, is expressed at high levels in the developing heart. Mech Dev 80:77-86

Showing the most recent 10 out of 13 publications