Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
4
pubmed:dateCreated
2007-11-22
pubmed:abstractText
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.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Nov
pubmed:issn
0896-6273
pubmed:author
pubmed:issnType
Print
pubmed:day
21
pubmed:volume
56
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
604-20
pubmed:dateRevised
2009-11-19
pubmed:meshHeading
pubmed-meshheading:18031680-Animals, pubmed-meshheading:18031680-Cell Differentiation, pubmed-meshheading:18031680-Cells, Cultured, pubmed-meshheading:18031680-Efferent Pathways, pubmed-meshheading:18031680-Enzyme Inhibitors, pubmed-meshheading:18031680-Gene Expression Regulation, Developmental, pubmed-meshheading:18031680-Genetic Testing, pubmed-meshheading:18031680-Growth Cones, pubmed-meshheading:18031680-MAP Kinase Signaling System, pubmed-meshheading:18031680-Male, pubmed-meshheading:18031680-Mice, pubmed-meshheading:18031680-Mice, Inbred C57BL, pubmed-meshheading:18031680-Mice, Inbred DBA, pubmed-meshheading:18031680-Mice, Transgenic, pubmed-meshheading:18031680-Microtubules, pubmed-meshheading:18031680-Motor Neurons, pubmed-meshheading:18031680-Mutation, pubmed-meshheading:18031680-Paclitaxel, pubmed-meshheading:18031680-Spinal Cord, pubmed-meshheading:18031680-Tubulin Modulators, pubmed-meshheading:18031680-p38 Mitogen-Activated Protein Kinases, pubmed-meshheading:18031680-ral Guanine Nucleotide Exchange Factor
pubmed:year
2007
pubmed:articleTitle
The ubiquitin ligase Phr1 regulates axon outgrowth through modulation of microtubule dynamics.
pubmed:affiliation
Gene Expression Laboratory, The Salk Institute for Biological Studies, La Jolla, CA 92037, USA.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't, Research Support, N.I.H., Extramural