Abstract

The purpose of this research program is to study roles for serotonin (5-HT) in mouse craniofacial development and to assess the teratogenic potential of serotonergic drugs. We will investigate possible sites of action of 5- HT, its binding protein (serotonin binding protein, SBP) and receptors in epithelial and mesenchyme of the craniofacial region using light and electron microscopic techniques. Direct effects of 5-HT on proliferation, migration and chondrogenic differentiation of neural crest-derived mesenchyme will be studied in cell culture using a variety of cellular and molecular techniques. We will also analyze effects of 5-HT or related drug on cell proliferation in the neuroepithelium of the cranial neural folds, the underlying mesenchyme, and in epithelia of the craniofacial region. Whole embryo culture will be used to determine dose-response relationships and critical periods of exposure for developmental defects produced by 5-HT uptake inhibitors and receptor analogs. These studies will aid in our understanding of the functional importance of 5-HT in morphogenesis generally and will specifically address it role in epithelial-mesenchyme interactions of the developing craniofacial region.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
Eunice Kennedy Shriver National Institute of Child Health & Human Development (NICHD)
Type
Research Project (R01)
Project #
5R01HD022052-06
Application #
3321319
Study Section
Oral Biology and Medicine Subcommittee 1 (OBM)
Project Start
1986-09-01
Project End
1994-03-31
Budget Start
1992-04-01
Budget End
1994-03-31
Support Year
6
Fiscal Year
1992
Total Cost
Indirect Cost

  Institution

Name
University of North Carolina Chapel Hill
Department
Type
Schools of Medicine
DUNS #
078861598
City
Chapel Hill
State
NC
Country
United States
Zip Code
27599

  Publications

Buznikov, G A; Lambert, H W; Lauder, J M (2001) Serotonin and serotonin-like substances as regulators of early embryogenesis and morphogenesis. Cell Tissue Res 305:177-86
Lambert, H W; Weiss, E R; Lauder, J M (2001) Activation of 5-HT receptors that stimulate the adenylyl cyclase pathway positively regulates IGF-I in cultured craniofacial mesenchymal cells. Dev Neurosci 23:70-7
Lauder, J M; Wilkie, M B; Wu, C et al. (2000) Expression of 5-HT(2A), 5-HT(2B) and 5-HT(2C) receptors in the mouse embryo. Int J Dev Neurosci 18:653-62
Lauder, J M; Liu, J; Grayson, D R (2000) In utero exposure to serotonergic drugs alters neonatal expression of 5-HT(1A) receptor transcripts: a quantitative RT-PCR study. Int J Dev Neurosci 18:171-6
Moiseiwitsch, J R (2000) The role of serotonin and neurotransmitters during craniofacial development. Crit Rev Oral Biol Med 11:230-9
Lambert, H W; Lauder, J M (1999) Serotonin receptor agonists that increase cyclic AMP positively regulate IGF-I in mouse mandibular mesenchymal cells. Dev Neurosci 21:105-12
Moiseiwitsch, J R; Raymond, J R; Tamir, H et al. (1998) Regulation by serotonin of tooth-germ morphogenesis and gene expression in mouse mandibular explant cultures. Arch Oral Biol 43:789-800
Moiseiwitsch, J R; Lauder, J M (1997) Regulation of gene expression in cultured embryonic mouse mandibular mesenchyme by serotonin antagonists. Anat Embryol (Berl) 195:71-8
Buznikov, G A; Shmukler, Iu B; Lowder, J M (1997) [Changes in the physiological role of the neurotransmitters during individual development] Ross Fiziol Zh Im I M Sechenova 83:1-15
Moiseiwitsch, J R; Lauder, J M (1996) Stimulation of murine tooth development in organotypic culture by the neurotransmitter serotonin. Arch Oral Biol 41:161-5

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