The ultimate aim of this grant is to identify and modify the regulatory factors of the human fetal keratinocyte prior to commitment toward organ development and terminal differentiation. Human fetal skin will be transplanted to nude mice where the normal human developmental sequence can be evaluated and modified. In addition in-vitro fetal keratinocyte culture systems will be developed to identify mechanisms and modifiers of keratinocyte growth and differentiation which may differ between fetal and adult keratinocytes. By using these two systems, organ development and terminal differentiation of human fetal skin will be studied. By chemically manipulating human fetal epidermal development in both systems, the biological and biochemical responses of fetal keratinocytes during development will be studied. Once the normal process of fetal development is detailed in both systems, major perturbations will be introduced through recombinant grafts of epidermal and dermal tissues and eventually keratinocytes and fibroblasts. These grafts will be modulated by previously identified chemical mediators including 13-cis-retinoic acid. The inductive influences of development will be identified in detail. The inductive influences then will be applied to diseases of epidermal proliferation (ichthyosis, ectodermal dysplasia, psoriasis, epidermal nevi) and diseases of the dermal-epidermal junction (epidermolysis bullosa). Using combinations of mature, fetal and diseased tissues, analysis of disease-induced variations will be evaluated. Modifications of human fetal development by diseased tissues will identify abnormalities of cellular control in disease.

Agency
National Institute of Health (NIH)
Institute
Eunice Kennedy Shriver National Institute of Child Health & Human Development (NICHD)
Type
Research Project (R01)
Project #
1R01HD020996-01
Application #
3319574
Study Section
General Medicine A Subcommittee 2 (GMA)
Project Start
1986-01-01
Project End
1988-12-31
Budget Start
1986-01-01
Budget End
1986-12-31
Support Year
1
Fiscal Year
1986
Total Cost
Indirect Cost
Name
University of Rochester
Department
Type
Schools of Medicine
DUNS #
208469486
City
Rochester
State
NY
Country
United States
Zip Code
14627
Colbert, M C; McCoon, P E; Day, K H et al. (1990) Monoclonal antibodies to two different epitopes in a 30-kD CNBr peptide of the K1 and K2 keratins. J Invest Dermatol 95:647-52
Haake, A R; Lane, A T (1989) Retention of differentiated characteristics in human fetal keratinocytes in vitro. In Vitro Cell Dev Biol 25:592-600
Lane, A T; Scott, G A; Day, K H (1989) Development of human fetal skin transplanted to the nude mouse. J Invest Dermatol 93:787-91
Lane, A T (1986) Human fetal skin development. Pediatr Dermatol 3:487-91