PMID- 20576928 OWN - NLM STAT- MEDLINE DCOM- 20110427 LR - 20220224 IS - 1460-2199 (Electronic) IS - 1047-3211 (Print) IS - 1047-3211 (Linking) VI - 21 IP - 2 DP - 2011 Feb TI - L1 and CHL1 Cooperate in Thalamocortical Axon Targeting. PG - 401-12 LID - 10.1093/cercor/bhq115 [doi] AB - 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. FAU - Demyanenko, Galina P AU - Demyanenko GP AD - Department of Biochemistry and Biophysics, University of North Carolina School of Medicine, Chapel Hill, NC 27599, USA. FAU - Siesser, Priscila F AU - Siesser PF FAU - Wright, Amanda G AU - Wright AG FAU - Brennaman, Leann H AU - Brennaman LH FAU - Bartsch, Udo AU - Bartsch U FAU - Schachner, Melitta AU - Schachner M FAU - Maness, Patricia F AU - Maness PF LA - eng GR - MH064056/MH/NIMH NIH HHS/United States GR - NS049109/NS/NINDS NIH HHS/United States PT - Journal Article PT - Research Support, N.I.H., Extramural PT - Research Support, Non-U.S. Gov't DEP - 20100624 PL - United States TA - Cereb Cortex JT - Cerebral cortex (New York, N.Y. : 1991) JID - 9110718 RN - 0 (Amino Acids) RN - 0 (Cell Adhesion Molecules) RN - 0 (Chl1 protein, mouse) RN - 0 (Ephrin-A5) RN - 0 (Luminescent Proteins) RN - 0 (Neural Cell Adhesion Molecule L1) RN - 0 (dolaisoleucine) RN - EC 2.7.10.1 (Receptors, Eph Family) SB - IM MH - Amino Acids/metabolism MH - Animals MH - Axons/drug effects/*physiology/ultrastructure MH - Cell Adhesion Molecules/deficiency/*metabolism MH - Cells, Cultured MH - Cerebral Cortex/cytology/*metabolism MH - Embryo, Mammalian MH - Ephrin-A5/pharmacology MH - Gene Expression Regulation/drug effects/genetics MH - Growth Cones/physiology MH - Humans MH - Immunoprecipitation/methods MH - Luminescent Proteins/genetics MH - Mice MH - Mice, Inbred C57BL MH - Mice, Transgenic MH - Neural Cell Adhesion Molecule L1/deficiency/*metabolism MH - Neural Pathways/*physiology MH - Neurons/cytology/drug effects/physiology MH - Receptors, Eph Family/genetics/metabolism MH - Thalamus/cytology/*metabolism MH - Transfection/methods PMC - PMC3020587 EDAT- 2010/06/26 06:00 MHDA- 2011/04/28 06:00 PMCR- 2012/02/01 CRDT- 2010/06/26 06:00 PHST- 2010/06/26 06:00 [entrez] PHST- 2010/06/26 06:00 [pubmed] PHST- 2011/04/28 06:00 [medline] PHST- 2012/02/01 00:00 [pmc-release] AID - bhq115 [pii] AID - 10.1093/cercor/bhq115 [doi] PST - ppublish SO - Cereb Cortex. 2011 Feb;21(2):401-12. doi: 10.1093/cercor/bhq115. Epub 2010 Jun 24.