Discoidin domain receptor 1 functions in axon extension of cerebellar granule neurons
AUTOR(ES)
Bhatt, Rupal S.
FONTE
Cold Spring Harbor Laboratory Press
RESUMO
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 β-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.
ACESSO AO ARTIGO
http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=316891Documentos Relacionados
- A functional role for the two-pore domain potassium channel TASK-1 in cerebellar granule neurons
- A non-inactivating K+ current sensitive to muscarinic receptor activation in rat cultured cerebellar granule neurons.
- The discoidin domain receptor tyrosine kinase DDR1 in arterial wound repair
- Synaptic activation of NF-kappa B by glutamate in cerebellar granule neurons in vitro.
- Discoidin Domain Receptor 1 Tyrosine Kinase Has an Essential Role in Mammary Gland Development