Abstract:
:To discover new genes involved in axon navigation, we conducted a forward genetic screen for recessive alleles affecting motor neuron pathfinding in GFP reporter mice mutagenized with ENU. In Magellan mutant embryos, motor axons were error prone and wandered inefficiently at choice points within embryos, but paradoxically responded to guidance cues with normal sensitivity in vitro. We mapped the Magellan mutation to the Phr1 gene encoding a large multidomain E3 ubiquitin ligase. Phr1 is associated with the microtubule cytoskeleton within neurons and selectively localizes to axons but is excluded from growth cones. Motor and sensory neurons from Magellan mutants display abnormal morphologies due to a breakdown in the polarized distribution of components that segregate between axons and growth cones. The Magellan phenotype can be reversed by stabilizing microtubules with taxol or inhibiting p38MAPK activity. Thus, efficacious pathfinding requires Phr1 activity for coordinating the cytoskeletal organization that distinguishes axons from growth cones.
journal_name
Neuronjournal_title
Neuronauthors
Lewcock JW,Genoud N,Lettieri K,Pfaff SLdoi
10.1016/j.neuron.2007.09.009subject
Has Abstractpub_date
2007-11-21 00:00:00pages
604-20issue
4eissn
0896-6273issn
1097-4199pii
S0896-6273(07)00707-6journal_volume
56pub_type
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