L1 and CHL1 Cooperate in Thalamocortical Axon Targeting.
Neural cell adhesion molecule close homolog of L1 (CHL1) is a regulator of topographic targeting of thalamic axons to the somatosensory cortex (S1) but little is known about its cooperation with other L1 class molecules. To investigate this, CHL1(-/-)/L1(-/y) double mutant mice were generated and analyzed for thalamocortical axon topography. Double mutants exhibited a striking posterior shift of axons from motor thalamic nuclei to the visual cortex (V1), which was not observed in single mutants. In wild-type (WT) embryos, L1 and CHL1 were coexpressed in the dorsal thalamus (DT) and on fibers along the thalamocortical projection in the ventral telencephalon and cortex. L1 and CHL1 colocalized on growth cones and neurites of cortical and thalamic neurons in culture. Growth cone collapse assays with WT and mutant neurons demonstrated a requirement for L1 and CHL1 in repellent responses to EphrinA5, a guidance factor for thalamic axons. L1 coimmunoprecipitated with the principal EphrinA5 receptors expressed in the DT (EphA3, EphA4, and EphA7), whereas CHL1 associated selectively with EphA7. These results implicate a novel mechanism in which L1 and CHL1 interact with individual EphA receptors and cooperate to guide subpopulations of thalamic axons to distinct neocortical areas essential for thalamocortical connectivity.
Demyanenko
Galina P
GP
Department of Biochemistry and Biophysics, University of North Carolina School of Medicine, Chapel Hill, NC 27599, USA.
Siesser
Priscila F
PF
Wright
Amanda G
AG
Brennaman
Leann H
LH
Bartsch
Udo
U
Schachner
Melitta
M
Maness
Patricia F
PF
D000596:Amino Acids / Q000378:metabolism; D000818:Animals; D001369:Axons / Q000187:drug effects / Q000502:physiology* / Q000648:ultrastructure; D015815:Cell Adhesion Molecules / Q000172:deficiency / Q000378:metabolism*; D002478:Cells, Cultured; D002540:Cerebral Cortex / Q000166:cytology / Q000378:metabolism*; D004622:Embryo, Mammalian; D036386:Ephrin-A5 / Q000494:pharmacology; D005786:Gene Expression Regulation / Q000187:drug effects / Q000235:genetics; D020439:Growth Cones / Q000502:physiology; D006801:Humans; D047468:Immunoprecipitation / Q000379:methods; D008164:Luminescent Proteins / Q000235:genetics; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D039842:Neural Cell Adhesion Molecule L1 / Q000172:deficiency / Q000378:metabolism*; D009434:Neural Pathways / Q000502:physiology*; D009474:Neurons / Q000166:cytology / Q000187:drug effects / Q000502:physiology; D036081:Receptors, Eph Family / Q000235:genetics / Q000378:metabolism; D013788:Thalamus / Q000166:cytology / Q000378:metabolism*; D014162:Transfection / Q000379:methods
D000596:Amino Acids; D015815:Cell Adhesion Molecules; C490649:Chl1 protein, mouse; D036386:Ephrin-A5; D008164:Luminescent Proteins; D039842:Neural Cell Adhesion Molecule L1; C098463:dolaisoleucine; D036081:Receptors, Eph Family