The long-term objective of this application is to understand the mechanisms regulating calcium metabolism and the role of calcium in tissue morphogenesis and physiological functions during embryonic development. Chick embryos will be used as the experimental model and the experiments will address the following specific aims: 1) to analyze the cellular and molecular mechanisms of calcium transport by extraembryonic membranes, i.e. the chorioallantoic membrane (CAM) and yolk sac (YS), using both cellular and cell-free approaches, with particular attention to the developmental and metabolic regulation of on of two calcium-binding proteins, transcalcin of the CAM and calbindin-D28K of the YS; 2) to elucidate the functional role of calcium and the mineralized matrix on cell differentiation in intramembranous bone development, in particular the possible mediating role of transforming growth factor beta; and 3) to determine the cellular pathways, In particular cellular calcium handling, involved in abnormal cardiovascular functions induced by systemic calcium deficiency during development. Chick embryos are uniquely suited for these studies since by long-term culture without the eggshell, their primary calcium source, they may be rendered highly calcium deficient. By comparing normal and shell-less (SL) embryos with respect to the above parameters, significant insights may be gained into the functional importance of calcium in embryogenesis. In summary, the studies proposed here should provide information on how Ca is translocated into the developing embryo to meet its needs, how systemic Ca homeostasis is regulated, and how its proper maintenance is important to skeletal development and cardiovascular functions. This multi-targeted project is realistically based on the overall research interests and demonstrated strength of the laboratory, and is expected to yield information useful and relevant to the general areas of fetal development, and skeletal and cardiovascular biology.

Agency
National Institute of Health (NIH)
Institute
Eunice Kennedy Shriver National Institute of Child Health & Human Development (NICHD)
Type
Research Project (R01)
Project #
5R01HD015822-12
Application #
2197250
Study Section
Oral Biology and Medicine Subcommittee 1 (OBM)
Project Start
1981-09-15
Project End
1997-02-28
Budget Start
1995-03-01
Budget End
1996-02-29
Support Year
12
Fiscal Year
1995
Total Cost
Indirect Cost
Name
Thomas Jefferson University
Department
Orthopedics
Type
Schools of Medicine
DUNS #
061197161
City
Philadelphia
State
PA
Country
United States
Zip Code
19107
McAleer, M F; Tuan, R S (2001) Metallothionein overexpression in human trophoblastic cells protects against cadmium-induced apoptosis. In Vitr Mol Toxicol 14:25-42
McAleer, M F; Tuan, R S (2001) Metallothionein protects against severe oxidative stress-induced apoptosis of human trophoblastic cells. In Vitr Mol Toxicol 14:219-31
Oberlender, S A; Tuan, R S (2000) Application of functional blocking antibodies. N-cadherin and chick embryonic limb development. Methods Mol Biol 137:37-42
LeClair, E E; Tuan, R S (2000) Quail-chick transplantation in the embryonic limb bud. Methods Mol Biol 135:387-96
Tuan, R S (2000) mRNA and protein co-localization on tissue sections by sequential, colorimetric in situ hybridization and immunohistochemistry. Methods Mol Biol 137:117-24
Denker, A E; Haas, A R; Nicoll, S B et al. (1999) Chondrogenic differentiation of murine C3H10T1/2 multipotential mesenchymal cells: I. Stimulation by bone morphogenetic protein-2 in high-density micromass cultures. Differentiation 64:67-76
Hershberger, M E; Tuan, R S (1999) Functional analysis of placental 57-kDa Ca(2+)-binding protein: overexpression and downregulation in a trophoblastic cell line. Dev Biol 215:107-17
Shah, A K; Lazatin, J; Sinha, R K et al. (1999) Mechanism of BMP-2 stimulated adhesion of osteoblastic cells to titanium alloy. Biol Cell 91:131-42
Haas, A R; Tuan, R S (1999) Chondrogenic differentiation of murine C3H10T1/2 multipotential mesenchymal cells: II. Stimulation by bone morphogenetic protein-2 requires modulation of N-cadherin expression and function. Differentiation 64:77-89
Shah, A K; Sinha, R K; Hickok, N J et al. (1999) High-resolution morphometric analysis of human osteoblastic cell adhesion on clinically relevant orthopedic alloys. Bone 24:499-506

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