Coordinated functions of Netrin-1 and Class 3 secreted Semaphorins in the guidance of reciprocal septohippocampal connections.
An essential characteristic of the CNS function is the formation of reciprocal connections between brain areas. Although the mechanisms controlling the establishment of neuronal connections are being determined, very little is known about the development of reciprocal connections, which often course along identical pathways. Here, we show that Netrin-1, expressed along the fimbria, chemoattracts both septohippocampal and hippocamposeptal fibers. Moreover, we show that both Semaphorins 3A and 3F expressed in regions nearby the septum prevent the growth of septal axons into these regions. Blocking experiments with recombinant ecto-Neuropilins indicate that both Semaphorins 3A and 3F act cooperatively in the repulsion of septal axons. Furthermore, netrin-1-deficient mice develop a reduced septohippocampal projection. We conclude that the coordinated actions of Netrin-1 and Semaphorins 3A and 3F cooperate in the development of septohippocampal and hippocamposeptal connections, indicating that the same molecular cues serve the construction of reciprocal connections in both directions of growth.
Pascual
Marta
M
Department of Cell Biology, University of Barcelona, and IRBB/Barcelona Science Park, Barcelona 08028, Spain.
Pozas
Esther
E
Barallobre
María José
MJ
Tessier-Lavigne
Marc
M
Soriano
Eduardo
E
D000818:Animals; D002454:Cell Differentiation / Q000502:physiology; D002478:Cells, Cultured; D018920:Coculture Techniques; D005333:Fetus; D020712:Fornix, Brain / Q000166:cytology / Q000196:embryology / Q000378:metabolism; D018507:Gene Expression Regulation, Developmental / Q000235:genetics; D020439:Growth Cones / Q000378:metabolism* / Q000648:ultrastructure; D006624:Hippocampus / Q000166:cytology / Q000196:embryology* / Q000378:metabolism; D008565:Membrane Proteins / Q000037:antagonists & inhibitors / Q000378:metabolism; D051379:Mice; D018345:Mice, Knockout; D009414:Nerve Growth Factors / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D009419:Nerve Tissue Proteins / Q000037:antagonists & inhibitors / Q000378:metabolism; D000075388:Netrin-1; D009434:Neural Pathways / Q000166:cytology / Q000196:embryology* / Q000378:metabolism; D039921:Neuropilins / Q000378:metabolism; D040121:Semaphorin-3A / Q000037:antagonists & inhibitors / Q000378:metabolism; D039961:Semaphorins / Q000037:antagonists & inhibitors / Q000378:metabolism / Q000502:physiology*; D012686:Septal Nuclei / Q000166:cytology / Q000196:embryology* / Q000378:metabolism; D025521:Tumor Suppressor Proteins
D008565:Membrane Proteins; D009414:Nerve Growth Factors; D009419:Nerve Tissue Proteins; D039921:Neuropilins; C000617353:Ntn1 protein, mouse; C491229:Sema3f protein, mouse; D040121:Semaphorin-3A; D039961:Semaphorins; D025521:Tumor Suppressor Proteins; D000075388:Netrin-1