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Publication : The absence of CD47 promotes nerve fiber growth from cultured ventral mesencephalic dopamine neurons.

First Author  Marschinke F Year  2012
Journal  PLoS One Volume  7
Issue  9 Pages  e45218
PubMed ID  23049778 Mgi Jnum  J:191950
Mgi Id  MGI:5463684 Doi  10.1371/journal.pone.0045218
Citation  Marschinke F, et al. (2012) The Absence of CD47 promotes nerve fiber growth from cultured ventral mesencephalic dopamine neurons. PLoS One 7(9):e45218
abstractText  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 SIRPalpha nor through TSP-1 since similar outgrowth was found in SIRPalpha 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.
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