The overall objective of this application is to understand the regulation of embryonic calcium metabolism with specific emphasis on the process of transplacental calcium transport. The system chosen for the proposed studies is the chick embryonic chorioallantoic membrane (CAM) which represents the avian equivalent of the placental unit and is responsible for the translocation of eggshell calcium into the embryonic circulation during development. The projects described in this proposal aim to elucidate the biochemical, cellular, and molecular mechanisms regulating the CAM calcium transport function. Our approach is to study the transport-associated proteins (e.g. calcium-binding protein, CaBP; and Ca2+-ATPase) previously identified in this laboratory as functional marker molecules for the calcium transport process. Specifically, we plan to first characterize and localize at a subcellular level these components and analyze their functional involvement and mechanistic role(s) in CAM calcium transport. Secondly, we will study the cellular, biochemical, and molecular events leading to the regulation of CaBP expression during normal embryonic development and under experimentally induced conditions of vitamin K and/or calcium deficiency. We believe that the experiments proposed here will define the functional roles of these marker molecules in CAM calcium transport and provide fundamental information on the mechanisms regulating an important physiological function, transplacental calcium transport, of the developing vertebrate embryo.

Agency
National Institute of Health (NIH)
Institute
Eunice Kennedy Shriver National Institute of Child Health & Human Development (NICHD)
Type
Research Project (R01)
Project #
7R01HD015822-06
Application #
3313279
Study Section
Cellular Biology and Physiology Subcommittee 1 (CBY)
Project Start
1981-09-15
Project End
1991-06-30
Budget Start
1988-07-01
Budget End
1989-06-30
Support Year
6
Fiscal Year
1988
Total Cost
Indirect Cost
Name
Thomas Jefferson University
Department
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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