For a nervous system to be wired into proper neuronal circuits, the axons need be guided to the correct targets and the dendrites must have the correct branching patterns. Relative little is known about the molecular basis for dendrite development. Recently, two evolutionarily conserved proteins, Trc and Fry, have been identified as essential players for dendritic branching and tiling. The goal of the proposal is to identify and characterize additional gene products in this core signaling program. Several lines of evidence suggest that Mats/Dmob1, a member of the conserved Mob family of proteins, may be involved in the Trc/Fry signaling pathway. I propose to test the hypothesis that Mats/Dmob1 functions as an activator to regulate Trc kinase activity. Genetic and biochemical analysis will also be performed to identify and characterize additional molecules implicated in the Trc/Fry signaling pathway in dendrite development. Given the strong conservation of this pathway across phylogeny, it is likely that our experiments will provide new insights into the mechanisms underlying dendrite development in vertebrates and may also lead to improved diagnosis and therapeutics of nervous system disorders caused by abnormal dendrites formation. ? ?
| Zheng, Yi; Wildonger, Jill; Ye, Bing et al. (2008) Dynein is required for polarized dendritic transport and uniform microtubule orientation in axons. Nat Cell Biol 10:1172-80 |
