The long term objective of this proposal is to study the role of the extracellular matrix (ECH) in the differentiation of embryonic organs. The organ of choice is the embryonic skin of the chick and the ECM components selected are the sulfated proteoglycans. Specifically we want to characterize the various proteoglycans which we have identified in embryonic skin. In so doing we will pursue 4 specific aims: (1) We will test the hypothesis that the various sulfated proteoglycans of the embryonic skin have different core proteins. This we propose to do by generating and characterizing monoclonal antibodies to the various proteoglycans. (2) We will use these antibodies to purify the various proteoglycans and to characterize them in terms of their glycosaminoglycan side chains. (3) We will analyze the temporal and spatial distribution of the normal and the scaleless mutant embryo which lacks feathers and scales. The distribution of the individual proteoglycans will be compared with that of other ECM macromolecules. (4) We will investigate the possibility that these proteoglycans may be present in other organs, which like the skin, depend on tissue interactions for their normal development. The organs tested will be the kidney, lung, thyroid and conjunctival papillae, and limbs. Although certain ECM molecules have been examined in the developing skin, proteoglycans have not been investigated in great detail. Information gained on the structure and distribution of proteoglycans in the developing skin may help us understand the role of this ECM component not only in the development of the skin but also in the development of other organs which depend on epithelial-mesenchymal interactions for their successful development. The analysis of a mutant in which skin morphogenesis is abnormal as a result of an interruption in the normal interactions between the epithelium and the mesenchyme may help us understand the mechanisms involved in the interactions. Such an analysis may also help us understand other abnormal developmental processes which result from either a genetic or teratological insult.

Agency
National Institute of Health (NIH)
Institute
Eunice Kennedy Shriver National Institute of Child Health & Human Development (NICHD)
Type
Research Project (R01)
Project #
7R01HD022050-01
Application #
3321308
Study Section
Pathobiochemistry Study Section (PBC)
Project Start
1986-01-01
Project End
1987-12-31
Budget Start
1986-01-01
Budget End
1986-12-31
Support Year
1
Fiscal Year
1986
Total Cost
Indirect Cost
Name
Sanford-Burnham Medical Research Institute
Department
Type
DUNS #
009214214
City
La Jolla
State
CA
Country
United States
Zip Code
92037
Song, H; Wang, Y; Goetinck, P F (1996) Fibroblast growth factor 2 can replace ectodermal signaling for feather development. Proc Natl Acad Sci U S A 93:10246-9
Baciu, P C; Goetinck, P F (1995) Protein kinase C regulates the recruitment of syndecan-4 into focal contacts. Mol Biol Cell 6:1503-13
Binette, F; Cravens, J; Kahoussi, B et al. (1994) Link protein is ubiquitously expressed in non-cartilaginous tissues where it enhances and stabilizes the interaction of proteoglycans with hyaluronic acid. J Biol Chem 269:19116-22
Baciu, P C; Acaster, C; Goetinck, P F (1994) Molecular cloning and genomic organization of chicken syndecan-4. J Biol Chem 269:696-703
Goetinck, P F (1991) Proteoglycans in development. Curr Top Dev Biol 25:111-31
Lever-Fischer, P L; Goetinck, P F (1988) Identification and characterization of a proteoglycan in embryonic chicken skin that can interact with hyaluronic acid. Arch Biochem Biophys 263:45-58
Goetinck, P F; Carlone, D L (1988) Altered proteoglycan synthesis disrupts feather pattern formation in chick embryonic skin. Dev Biol 127:179-86