Recent advances in cell and molecular biology suggest that a number of cell surface adhesion and extracellular matrix (ECM) molecules are important for neuronal growth and guidance. The actual role of these molecules, however, must ultimately be determined using in vivo studies. The proposed research will examine the role of these molecules in vivo, using the sympathetic preganglionic projections of the chick. this neural system is ideal for such studies because the anatomy is relatively simple, the development is well understood and the presumptive pathways of growing axons are predictable and accessible for perturbation. Proposed in vivo studies include: (1) the determination of the spatio- temporal expression of cell surface adhesion and ECM molecules that are known to promote neuronal growth in vitro. and (2) the use of functional blockers to examine the role of these molecules on axonal growth and guidance. Cell surface adhesion and ECM molecules will be revealed by immuno- and histochemical staining; their functions will be evaluated according to changes in patterns of preganglionic projections subsequent to local injection of functional blockers to the pathway of preganglionic axons. The role of these molecules on neuronal specificity, growth, and fasciculation will be examined further under less complex and more controlled conditions, by studying the effects of functional blockers on identified neurons grown on tissue explants or cryostat sections in vitro. Finally, as a first step towards identifying novel guidance molecules in sympathetic preganglionic outgrowth, the specificity of preganglionic projections on tissue explants or cryostat sections obtained from embryos of different developmental stages will be examined to provide information of where and when molecular cues are expressed. These systematic studies on the sympathetic nervous system of the chick should provide important insights on axonal guidance mechanisms, knowledge that is extremely difficult to obtain from the complex central nervous system.

Agency
National Institute of Health (NIH)
Institute
National Institute of Neurological Disorders and Stroke (NINDS)
Type
Research Project (R01)
Project #
5R01NS023916-06
Application #
3407970
Study Section
Neurology B Subcommittee 2 (NEUB)
Project Start
1989-09-29
Project End
1994-06-30
Budget Start
1991-09-01
Budget End
1994-06-30
Support Year
6
Fiscal Year
1991
Total Cost
Indirect Cost
Name
University of Pittsburgh
Department
Type
Schools of Medicine
DUNS #
053785812
City
Pittsburgh
State
PA
Country
United States
Zip Code
15213
Yip, J W; Yip, Y P; Capriotti, C (1998) Specific projections of sympathetic preganglionic neurons are not intrinsically determined by segmental origins of their cell bodies. J Neurobiol 35:371-8
Yip, J W; Yip, Y P; Capriotti, C (1998) Segmental specificity of chick sympathetic preganglionic projections is influenced by preganglionic neurons from neighboring spinal cord segments. J Neurosci 18:10473-80
Yip, J W (1996) Specificity of sympathetic preganglionic projections in the chick is influenced by the somitic mesoderm. J Neurosci 16:612-20
Spence, M S; Yip, J; Erickson, C A (1996) The dorsal neural tube organizes the dermamyotome and induces axial myocytes in the avian embryo. Development 122:231-41
Yip, J W; Yip, Y P; Capriotti, C (1995) The expression, origin and function of tenascin during peripheral nerve formation in the chick. Brain Res Dev Brain Res 86:297-310
Halfter, W; Yip, Y P; Yip, J W (1994) Axonin 1 is expressed primarily in subclasses of avian sensory neurons during outgrowth. Brain Res Dev Brain Res 78:87-101
Yip, J W; Yip, Y P (1992) Laminin--developmental expression and role in axonal outgrowth in the peripheral nervous system of the chick. Brain Res Dev Brain Res 68:23-33
Yip, J W; Yip, Y P (1990) Changes in fibronectin distribution in the developing peripheral nervous system of the chick. Brain Res Dev Brain Res 51:11-8
Yip, J W (1990) Identification of location and timing of guidance cues in sympathetic preganglionic axons of the chick. J Neurosci 10:2476-84