Involvement of Cajal-Retzius cells in robust and layer-specific regeneration of the entorhino-hippocampal pathways.
Severed adult CNS axons can extend over long distances when a permissive 'milieu', such as grafted Schwann cells or ensheathing cells, is provided. Moreover, functional blocking of endogenous inhibitory factors, such as Nogo-A or proteoglycans, enhances the regeneration of axotomized neurons. Here we examine whether guidance cues available during the development of axonal pathways could also potentiate the regeneration of lesioned adult circuits. The Cajal-Retzius cells in the hippocampus are transient pioneer neurons that guide entorhino-hippocampal afferents to their target layers. By using an in vitro model of axotomy of the entorhino-hippocampal pathway we show that Cajal-Retzius cells triggered the regeneration of the axotomized entorhino-hippocampal pathway. Furthermore, the regrowth induced by Cajal-Retzius cells was robust and its pattern was indistinguishable from that of the unlesioned entorhino-hippocampal pathway. Thus, regenerating axons regrew in a layer-specific fashion towards the appropriate target layers, making synaptic contacts with target pyramidal neurons. Interestingly, the ability of lesioned entorhinal axons to regrow was maintained for at least 9 days after axotomy. These results show that the growth-promoting cells controlling the development of neural circuits will be a relevant approach to promoting the regeneration of lesioned adult CNS pathways.
del Río
José A
JA
Department of Cell Biology, Faculty of Biology, and Neuroscience Research Center (CERN), University of Barcelona, Diagonal 645, 08028 Barcelona, Spain. jario@porthos.bio.ub.es
Solé
Marta
M
Borrell
Víctor
V
Martínez
Albert
A
Soriano
Eduardo
E
D000375:Aging / Q000502:physiology; D000818:Animals; D000831:Animals, Newborn; D019771:Axotomy; D019521:Body Patterning / Q000502:physiology; D002450:Cell Communication / Q000502:physiology; D018920:Coculture Techniques; D003463:Cues; D018728:Entorhinal Cortex / Q000254:growth & development* / Q000293:injuries / Q000502:physiology; D020439:Growth Cones / Q000502:physiology / Q000648:ultrastructure; D006133:Growth Substances / Q000378:metabolism; D006624:Hippocampus / Q000254:growth & development* / Q000293:injuries / Q000502:physiology; D008239:Lysine / Q000031:analogs & derivatives*; D051379:Mice; D008815:Mice, Inbred Strains; D008854:Microscopy, Electron; D009416:Nerve Regeneration / Q000502:physiology*; D009434:Neural Pathways / Q000254:growth & development* / Q000293:injuries / Q000502:physiology; D009473:Neuronal Plasticity / Q000502:physiology; D009924:Organ Culture Techniques; D017729:Presynaptic Terminals / Q000502:physiology* / Q000648:ultrastructure; D017966:Pyramidal Cells / Q000502:physiology* / Q000648:ultrastructure; D013234:Stem Cells / Q000502:physiology* / Q000648:ultrastructure
D006133:Growth Substances; C013411:biocytin; D008239:Lysine