Close homolog of L1 modulates area-specific neuronal positioning and dendrite orientation in the cerebral cortex.
We show that the neural cell recognition molecule Close Homolog of L1 (CHL1) is required for neuronal positioning and dendritic growth of pyramidal neurons in the posterior region of the developing mouse neocortex. CHL1 was expressed in pyramidal neurons in a high-caudal to low-rostral gradient within the developing cortex. Deep layer pyramidal neurons of CHL1-minus mice were shifted to lower laminar positions in the visual and somatosensory cortex and developed misoriented, often inverted apical dendrites. Impaired migration of CHL1-minus cortical neurons was suggested by strikingly slower rates of radial migration in cortical slices, failure to potentiate integrin-dependent haptotactic cell migration in vitro, and accumulation of migratory cells in the intermediate and ventricular/subventricular zones in vivo. The restriction of CHL1 expression and effects of its deletion in posterior neocortical areas suggests that CHL1 may regulate area-specific neuronal connectivity and, by extension, function in the visual and somatosensory cortex.
Demyanenko
Galina P
GP
Department of Biochemistry and Biophysics, University of North Carolina School of Medicine, Chapel Hill, NC 27599, USA.
Schachner
Melitta
M
Anton
Eva
E
Schmid
Ralf
R
Feng
Guoping
G
Sanes
Joshua
J
Maness
Patricia F
PF
D000818:Animals; D000831:Animals, Newborn; D015153:Blotting, Western / Q000379:methods; D001973:Bromodeoxyuridine / Q000378:metabolism; D002232:Carbocyanines / Q000378:metabolism; D015815:Cell Adhesion Molecules; D002452:Cell Count / Q000379:methods; D002465:Cell Movement / Q000502:physiology; D002540:Cerebral Cortex / Q000166:cytology* / Q000378:metabolism / Q000502:physiology; D003712:Dendrites / Q000502:physiology*; D004622:Embryo, Mammalian; D005455:Fluorescent Antibody Technique / Q000379:methods; D018507:Gene Expression Regulation, Developmental / Q000502:physiology*; D066298:In Vitro Techniques; D019012:Integrin beta1 / Q000378:metabolism; D008164:Luminescent Proteins / Q000096:biosynthesis / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D018613:Microscopy, Confocal / Q000379:methods; D011506:Proteins / Q000235:genetics / Q000502:physiology*; D017966:Pyramidal Cells / Q000502:physiology*; D013997:Time Factors
C035005:3,3'-dihexadecylindocarbocyanine; D002232:Carbocyanines; D015815:Cell Adhesion Molecules; C490649:Chl1 protein, mouse; D019012:Integrin beta1; D008164:Luminescent Proteins; D011506:Proteins; D001973:Bromodeoxyuridine