While it was later also detected in immune cells like monocytes, granulocytes and macrophages. The neurotrophic factor brain-derived neurotrophic factor, which is potent for dopamine neurons, exerts its effect through SHP-2 by affecting the phosphorylation of SIRPa. Moreover, CD47 act as a receptor for thrombospondin-1, belonging to a family of extracellular matrix glycoproteins, which is widely expressed in the developing and adult brain and exert a wide range of effects on cell behavior such as migration, adhesion, and neurite outgrowth. Overexpression of CD47 improves dendritic growth and affects synaptic proteins, while CD47 gene deletion improves regeneration in the spinal cord. Thus, the results gives contradicting information and to further elucidate the role of CD47 in affecting nerve fiber formation, especially the non-glial-associated nerve fiber growth, this study was undertaken to investigate nerve fiber growth in organotypic slice cultures of fetal ventral mesencephalon derived from CD47 gene deleted mice and to study the effects of TSP-1 and SIRPa. The non-glial-associated nerve fibers are found in organotypic slice cultures when the tissue is attached to the substrate already at plating. It has been demonstrated that the age of the tissue at plating influences the presence of the non-glial-associated growth such that the earlier the stage of the tissue at plating, the more robust is the expression. Therefore, E14 was used in the present study as an optimal time point for when the non-glialassociated growth is first developed and then retracted. The retraction might be interpreted as degeneration, however, this has not been possible to prove due to different time schedules for apoptotic markers at the cell body level and axon disruption, which occurs later. From previous ALK5 Inhibitor II ALK inhibitor studies, it appears to be a tight correlation between the astrocytic migration and the presence of non-glial-associated growth, such that when the astrocytes migrate, the non-glial-associated growth disappears earlier and it is stimulated when the astrocytes are inhibited. Thus, the correlation between the non-glial- and glialassociated nerve fibers appears always to end up in the more persistent glial-associated growth, but over different time schedule depending on treatment. Although this study has not included the glial-associated growth, due to difficulties to distinguish between the two growth patterns, because the non-glial-associated nerve fibers were too robust in the CD472/2 cultures, the presence of astrocytes was similar in all cultures. This is the first time that no sign of retraction of the non-glial-associated nerve fibers has been documented in the presence of astrocytic migration at 14 DIV, as found in the CD472/2 tissue cultures. Interestingly, the lack of CD47 enhanced both the length and density of the non-glialassociated nerve fibers, parameters that has never been affected before. To study possible mechanisms that promoted nerve fiber growth in the absence of CD47, cultures from the CD47 receptor SIRPa mutants were investigated. SIRPa is a transmembrane protein with an extracellular domain that binds to CD47 and a cytoplasmatic domain containing four tyrosine phosphorylation sites that serve as binding sites for the Src homology 2 domains of SHP-1 and SHP-2. The SIRPa mutant mouse has the normal extracellular domain, but truncated intracellular domain of the receptor and can thus not mediate the signaling following CD47 binding. SIRPa is highly expressed in neurons and enriched.