It is widely accepted that many aspects of CNS development are molded by events which occur in the sensory periphery and which are transmitted centrally. For the mammalian nervous system, such information transfer is epitomized by the influence of the rodent whisker field on the patterning of cell groups along the trigeminal neuraxis. To understand the events which are critical for such periphery-to-center relationships to unfold, it is imperative to gain a clear understanding of how the nervous system gets wired up with the periphery. The PI proposes to do this for the trigeminal system, focusing on the role of the neurotrophins (NTs) NGF, BDNF, NT-3, and NT-4 in the targeting of ganglion cell axons to specific compartments (e.g. whisker follicles) of the mystacial pad and to specific regions of the brainstem. Experiments are outlined to use available antibody probes and anatomical tracers to analyze the development of the whisker pad, and of the parallel morphogenesis of axons that innervate it. First the stages of trigeminal axon growth, and the sequential development of whisker pad will be determined. The expression of NTs and their receptors (NTRs) (trkA, trkB, trkC, p75NGFR) will be mapped during the time of their peak expression in the trigeminal system, and as they are down regulated to basal levels. Spatial and temporal correlations will be made between the localization of NTs in specific cutaneous fields, and the expression of the corresponding NTRs on afferents to that field. Similar correlations will be made in the trigeminal brainstem. Based on pilot data which show that NTs may also affect the growth mode (elongation vs. arborization) of trigeminal ganglion cell axons, we propose to directly test the effects of each of the NTs on the morphology of sensory neurons growing in culture. A corresponding in vivo paradigm will be used to administer NTs to the embryo before, during and after the period of normally-occurring cell death in order to test our understanding of the role of these important molecules in the living animals as it matures.

Agency
National Institute of Health (NIH)
Institute
National Institute of Neurological Disorders and Stroke (NINDS)
Type
Research Project (R01)
Project #
5R01NS027678-08
Application #
2771926
Study Section
Neurology B Subcommittee 2 (NEUB)
Program Officer
Chiu, Arlene Y
Project Start
1990-04-01
Project End
2000-11-30
Budget Start
1998-09-01
Budget End
2000-11-30
Support Year
8
Fiscal Year
1998
Total Cost
Indirect Cost
Name
Massachusetts Institute of Technology
Department
Other Basic Sciences
Type
Other Domestic Higher Education
DUNS #
City
Cambridge
State
MA
Country
United States
Zip Code
02139
Vercelli, A; Repici, M; Biasiol, S et al. (1999) Maturation of NADPH-d activity in the rat's barrel-field cortex and its relationship to cytochrome oxidase activity. Exp Neurol 156:294-315
Sendemir, E; Erzurumlu, R S; Jhaveri, S (1996) Differential expression of acetylcholinesterase in the developing barrel cortex of three rodent species. Cereb Cortex 6:377-87
Erzurumlu, R S; Jhaveri, S (1995) Target influences on the morphology of trigeminal axons. Exp Neurol 135:1-16
Li, Y; Erzurumlu, R S; Chen, C et al. (1994) Whisker-related neuronal patterns fail to develop in the trigeminal brainstem nuclei of NMDAR1 knockout mice. Cell 76:427-37
Erzurumlu, R S; McKay, R D; Jhaveri, S (1994) Morphological specification of trigeminal neurites depends on target fields. Brain Res Dev Brain Res 83:132-7
Erzurumlu, R S; Jhaveri, S; Takahashi, H et al. (1993) Target-derived influences on axon growth modes in cultures of trigeminal neurons. Proc Natl Acad Sci U S A 90:7235-9
Erzurumlu, R S; Jhaveri, S (1992) Trigeminal ganglion cell processes are spatially ordered prior to the differentiation of the vibrissa pad. J Neurosci 12:3946-55
Erzurumlu, R S; Jhaveri, S (1992) Emergence of connectivity in the embryonic rat parietal cortex. Cereb Cortex 2:336-52
Jhaveri, S; Erzurumlu, R S; Crossin, K (1991) Barrel construction in rodent neocortex: role of thalamic afferents versus extracellular matrix molecules. Proc Natl Acad Sci U S A 88:4489-93
Blue, M E; Erzurumlu, R S; Jhaveri, S (1991) A comparison of pattern formation by thalamocortical and serotonergic afferents in the rat barrel field cortex. Cereb Cortex 1:380-9