Discoidin domain receptor 1 functions in axon extension of cerebellar granule neurons
- PMID: 10970885
- PMCID: PMC316891
- DOI: 10.1101/gad.821600
Discoidin domain receptor 1 functions in axon extension of cerebellar granule neurons
Abstract
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 beta-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.
Figures
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References
-
- Alves F, Vogel W, Mossie K, Millauer B, Hofler H, Ullrich A. Distinct structural characteristics of discoidin I subfamily receptor tyrosine kinases and complementary expression in human cancer. Oncogene. 1995;10:609–618. - PubMed
-
- Brooks VB, Thach WT. Section 1: The nervous system, volume II. Motor control. In: Brooks VB, editor. Handbook of physiology. Bethesda, MD: American Physiological Society; 1981. pp. 877–946.
-
- Davis S, Gale NW, Aldrich TH, Maisonpierre PC, Lhotak V, Pawson T, Goldfarb M, Yancopoulos GD. Ligands for EPH-related receptor tyrosine kinases that require membrane attachment or clustering for activity. Science. 1994;266:816–819. - PubMed
-
- Eccles JC, Ito M, Szentágothai J. The cerebellum as a neuronal machine. New York, NY: Springer; 1967.
-
- Fiez JA. Cerebellar contributions to cognition. Neuron. 1996;16:13–15. - PubMed
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