Journal
GENES & DEVELOPMENT
Volume 14, Issue 17, Pages 2216-2228Publisher
COLD SPRING HARBOR LAB PRESS, PUBLICATIONS DEPT
DOI: 10.1101/gad.821600
Keywords
DDR; collagen; parallel fiber; axon extension; cerebellar granule neuron; retrovirus
Categories
Funding
- NCRR NIH HHS [P41 RR001192] Funding Source: Medline
- NIGMS NIH HHS [T32 GM007739] Funding Source: Medline
- NINDS NIH HHS [NS30532-05] Funding Source: Medline
Ask authors/readers for more resources
In the developing cerebellum, granule neuron axon outgrowth is a key step toward establishing proper connections with Purkinje neurons, the principal output neuron of the cerebellum. During a search for genes that function in this process, we identified a receptor tyrosine kinase discoidin domain receptor 1 (DDR1) expressed in granule cells throughout their development. Overexpression of a dominant-negative form of DDR1 in immature granule cells results in severe reduction of neurite outgrowth in vitro, in dissociated primary culture, and in vivo, in organotypic slices of neonatal cerebellum. Granule cells that fail to extend axons are positive for differentiation markers such as TAG-1 and the neuron-specific class III p-tubulin, suggesting that development is affected after granule cells commit to terminal differentiation. DDR1 activation appears to be mediated by its ligand, collagen, which is localized to the pial layer of the developing cerebellum, thereby leading to granule cell parallel fiber extension. Our results therefore indicate that collagen-DDR1 signaling is essential for granule neuron axon formation and further suggest a unique role of pia in cerebellar cortex histogenesis.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available