Document Detail


Targeting of the EphA4 tyrosine kinase receptor affects dorsal/ventral pathfinding of limb motor axons.
MedLine Citation:
PMID:  10887087     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
The Eph family of tyrosine kinase receptors has recently been implicated in various processes involving the detection of environmental cues such as axonal guidance, targeted cell migration and boundary formation. We have inactivated the mouse EphA4 gene to investigate its functions during development. Homozygous EphA4 mutant animals show peroneal muscular atrophy correlating with the absence of the peroneal nerve, the main dorsal nerve of the hindlimb. This phenotype is also observed, although with a lower penetrance, in heterozygotes. During normal hindlimb innervation, motor axons converge towards the sciatic plexus region at the base of the limb bud, where they must choose between dorsal and ventral trajectories within the limb. Among the axons emerging from the sciatic plexus, dorsal projections show higher levels of EphA4 protein than ventral axons. In EphA4 mutant mice, presumptive dorsal motor axons fail to enter the dorsal compartment of the limb and join the ventral nerve. Our data therefore suggest that the level of EphA4 protein in growing limb motor axons is involved in the selection of dorsal versus ventral trajectories, thus contributing to the topographic organisation of motor projections.
Authors:
F Helmbacher; S Schneider-Maunoury; P Topilko; L Tiret; P Charnay
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Development (Cambridge, England)     Volume:  127     ISSN:  0950-1991     ISO Abbreviation:  Development     Publication Date:  2000 Aug 
Date Detail:
Created Date:  2000-08-21     Completed Date:  2000-08-21     Revised Date:  2009-11-19    
Medline Journal Info:
Nlm Unique ID:  8701744     Medline TA:  Development     Country:  ENGLAND    
Other Details:
Languages:  eng     Pagination:  3313-24     Citation Subset:  IM    
Affiliation:
Unité 368 de l'Institut National de la Santé et de la Recherche Médicale, Ecole Normale Supérieure, 75230 Paris Cedex 05, France.
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MeSH Terms
Descriptor/Qualifier:
Animals
Axons / physiology*
Cell Line
Cell Movement
Cloning, Molecular
Fetal Proteins / genetics,  physiology*
Gene Targeting
Growth Cones / physiology
Hindlimb / embryology,  innervation
Limb Buds / innervation
Mesoderm
Mice
Motor Neurons / physiology*
Mutation
Neural Pathways / embryology,  physiology
Peroneal Nerve / embryology,  physiology
Phenotype
Receptor Protein-Tyrosine Kinases / genetics,  physiology*
Receptor, EphA4
Chemical
Reg. No./Substance:
0/Fetal Proteins; EC 2.7.10.1/Receptor Protein-Tyrosine Kinases; EC 2.7.10.1/Receptor, EphA4

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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