The absence of CD47 promotes nerve fiber growth from cultured ventral mesencephalic dopamine neurons
2012 (English)In: PLoS ONE, ISSN 1932-6203, Vol. 7, no 9, e45218- p.Article in journal (Refereed) Published
In ventral mesencephalic organotypic tissue cultures, two timely separated sequences of nerve fiber growth have been observed. The first appearing nerve fiber pattern is a long-distance outgrowth that occurs before astrocytes start to proliferate and migrate to form an astrocytic monolayer that finally surrounds the tissue slice. These long-distance growing nerve fibers are retracted as the astrocytes migrate, and are followed by a secondary outgrowth. The secondary outgrowth is persistent in time but reaches short distances, comparable with outgrowth seen from a dopaminergic graft implanted to the brain. The present study was focused on the interaction between the astrocytes and the long-distance growing non-glial associated nerve fibers. Cross talk between astroglia and neurite formation might occur through the integrin-associated protein CD47. CD47 serves as a ligand for signal regulatory protein (SIRP) alpha and as a receptor for the extracellular matrix protein thrombospondin-1 (TSP-1). Embryonic day 14 ventral mesencephalic tissue from CD47(+/+) and CD47(-/-) mice was used to investigate astrocytic migration and the tyrosine hydroxylase (TH) -positive outgrowth that occurred remote from the astrocytes. TH-immunohistochemistry demonstrated that the non-glial-associated nerve fiber outgrowth in CD47(-/-) cultures reached significantly longer distances and higher density compared to nerve fibers formed in CD47(+/+) cultures at 14 days in vitro. These nerve fibers often had a dotted appearance in CD47(+/+) cultures. No difference in the astrocytic migration was observed. Further investigations revealed that the presence of CD47 in control culture did neither hamper non-glial-associated growth through SIRP alpha nor through TSP-1 since similar outgrowth was found in SIRP alpha mutant cultures and in CD47(+/+) cultures treated with blocking antibodies against the TSP-1, respectively, as in the control cultures. In conclusion, long-distance growing nerve fiber formation is promoted by the absence of CD47, even though the presence of astrocytes is not inhibited.
Place, publisher, year, edition, pages
Public library of science , 2012. Vol. 7, no 9, e45218- p.
IdentifiersURN: urn:nbn:se:umu:diva-61571DOI: 10.1371/journal.pone.0045218ISI: 000309517300019OAI: oai:DiVA.org:umu-61571DiVA: diva2:581663