This research is intended to determine how specialized cell types become directed into specific pathways of cellular differentiation, using the rat salivary glands as an experimental model. It focuses on the transient secretory proteins of the perinatal submandibular gland, and on their transformation into mature acinar cells. The work will examine cells in the small ducts of the adult gland, since these alone continue to express the unique protein products of the perinatal cells. Antibodies to the perinatal proteins will be used to identify by immunocytochemistry the several cellular phenotypes recognizable in these ducts, and determining their capacity to participate in normal and trauma-induced cellular replacement, using 3H-thymidine incorporation and following the changes in the cells as they differentiate. Studies will be initiated to determine whether a similar perinatal system exists in humans, and if this might be relevant to the potential for cellular replacement therapies in human exocrine glands. This work will also approach the question of the function and regulatory control of an unusual membrane-associated protein (Protein D) found in the two cell types of the perinatal gland and in the serous demilune cells of the sublingual gland. The experiments will examine the hypotheses that Protein D is attached to the membrane by a glycophospholipid anchor and functions to package other proteins for secretion. Ultracentrifugation will be used to isolate secretion granules and biochemical methods will determine the nature of the membrane association. The kinetics of processing and secretion will be studied by immunogold electron microscope analysis, after rapid freezing and freeze- substitution. An approach to the regulation of the perinatal genes will be continued through a gene cloning analysis, by screening a cDNA expression library for Protein D clones and determining its sequence.

Agency
National Institute of Health (NIH)
Institute
National Institute of Dental & Craniofacial Research (NIDCR)
Type
Research Project (R01)
Project #
2R01DE006635-08
Application #
2129368
Study Section
Oral Biology and Medicine Subcommittee 1 (OBM)
Project Start
1983-08-01
Project End
1997-07-31
Budget Start
1995-09-15
Budget End
1996-07-31
Support Year
8
Fiscal Year
1995
Total Cost
Indirect Cost
Name
Howard University
Department
Anatomy/Cell Biology
Type
Schools of Medicine
DUNS #
056282296
City
Washington
State
DC
Country
United States
Zip Code
20059
Ball, W D; Mirels, L; Hand, A R (2003) Psp and Smgb: a model for developmental and functional regulation in the rat major salivary glands. Biochem Soc Trans 31:777-80
Man, Y G; Ball, W D; Marchetti, L et al. (2001) Contributions of intercalated duct cells to the normal parenchyma of submandibular glands of adult rats. Anat Rec 263:202-14
Mirels, L; Miranda, A J; Ball, W D (1998) Characterization of the rat salivary-gland B1-immunoreactive proteins. Biochem J 330 ( Pt 1):437-44
Denny, P C; Ball, W D; Redman, R S (1997) Salivary glands: a paradigm for diversity of gland development. Crit Rev Oral Biol Med 8:51-75
Hand, A R; Sivakumar, S; Barta, I et al. (1996) Immunocytochemical studies of cell differentiation during rat salivary gland development. Eur J Morphol 34:149-54
Man, Y G; Ball, W D; Culp, D J et al. (1995) Persistence of a perinatal cellular phenotype in submandibular glands of adult rat. J Histochem Cytochem 43:1203-15
Ball, W D; Hand, A R; Moreira, J E et al. (1993) The B1-immunoreactive proteins of the perinatal submandibular gland: similarity to the major parotid gland protein, RPSP. Crit Rev Oral Biol Med 4:517-24
Mirels, L; Ball, W D (1992) Neonatal rat submandibular gland protein SMG-A and parotid secretory protein are alternatively regulated members of a salivary protein multigene family. J Biol Chem 267:2679-87
Ball, W D; Hand, A R; Moreira, J E (1991) A neonatal secretory protein associated with secretion granule membranes in developing rat salivary glands. J Histochem Cytochem 39:1693-706
Moreira, J E; Ball, W D; Mirels, L et al. (1991) Accumulation and localization of two adult acinar cell secretory proteins during development of the rat submandibular gland. Am J Anat 191:167-84

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