Abstract

The objective of this grant is to define the role played by the signaling molecule collapsin-1 (semD, sema-III) in the developing nervous system. Collapsin-1 induces the collapse and paralysis of sensory growth cones and in collagen stabilized cultures acts as a repellent for sensory axons. During the course of the current funding period, the PI has compared the relative distributions of collapsin-1 expression with the trajectories of axon that are responsive to it. These studies have suggested that collapsin-1 plays a role in organizing axon trajectories in the skin, spinal cord, hindbrain, olfactory bulb and cerebellum. The PI will test these expectations by manipulating collapsin-1 function in vivo using a variety if misexpression, knockout and dominant negative strategies. Specifically, he will:
Aim 1 : study the guidance of selected axons in collapsin-1 knockout mice;
Aim 2 : study the relationship between the structure and function of the collapsin-1 receptor component neuropilin; and;
Aim 3 : study the role of collapsin-1 mediated guidance in chick embryos. Identifying repellent cues and understanding their roles in normal development may be an essential step towards obtaining axonal repair and establishing appropriate connectivity in damaged nervous tissue.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Institute of Neurological Disorders and Stroke (NINDS)
Type
Research Project (R01)
Project #
5R01NS026527-11
Application #
2891729
Study Section
Neurology B Subcommittee 2 (NEUB)
Program Officer
Leblanc, Gabrielle G
Project Start
1988-09-01
Project End
2002-04-30
Budget Start
1999-05-01
Budget End
2000-04-30
Support Year
11
Fiscal Year
1999
Total Cost
Indirect Cost

  Institution

Name
University of Pennsylvania
Department
Neurosciences
Type
Schools of Medicine
DUNS #
042250712
City
Philadelphia
State
PA
Country
United States
Zip Code
19104

  Publications

Twery, E Naomi; Raper, Jonathan A (2011) SDF1-induced antagonism of axonal repulsion requires multiple G-protein coupled signaling components that work in parallel. PLoS One 6:e18896
Chalasani, Sreekanth H; Sabol, Angela; Xu, Hong et al. (2007) Stromal cell-derived factor-1 antagonizes slit/robo signaling in vivo. J Neurosci 27:973-80
Jia, Li; Cheng, Lan; Raper, Jonathan (2005) Slit/Robo signaling is necessary to confine early neural crest cells to the ventral migratory pathway in the trunk. Dev Biol 282:411-21
Kreibich, Thomas A; Chalasani, Sreekanth H; Raper, Jonathan A (2004) The neurotransmitter glutamate reduces axonal responsiveness to multiple repellents through the activation of metabotropic glutamate receptor 1. J Neurosci 24:7085-95
Chalasani, Sreekanth H; Baribaud, Frederic; Coughlan, Christine M et al. (2003) The chemokine stromal cell-derived factor-1 promotes the survival of embryonic retinal ganglion cells. J Neurosci 23:4601-12
Chalasani, Sreekanth H; Sabelko, Kimberly A; Sunshine, Mary J et al. (2003) A chemokine, SDF-1, reduces the effectiveness of multiple axonal repellents and is required for normal axon pathfinding. J Neurosci 23:1360-71
Niclou, S P; Jia, L; Raper, J A (2000) Slit2 is a repellent for retinal ganglion cell axons. J Neurosci 20:4962-74
Renzi, M J; Wexler, T L; Raper, J A (2000) Olfactory sensory axons expressing a dominant-negative semaphorin receptor enter the CNS early and overshoot their target. Neuron 28:437-47
Renzi, M J; Feiner, L; Koppel, A M et al. (1999) A dominant negative receptor for specific secreted semaphorins is generated by deleting an extracellular domain from neuropilin-1. J Neurosci 19:7870-80
Miao, H Q; Soker, S; Feiner, L et al. (1999) Neuropilin-1 mediates collapsin-1/semaphorin III inhibition of endothelial cell motility: functional competition of collapsin-1 and vascular endothelial growth factor-165. J Cell Biol 146:233-42

Showing the most recent 10 out of 11 publications