Gas6 enhances human oligodendrocyte viability and maturation

Abstract

Oligodendrocyte development and survival occurs in response to signalling pathways activated by protein trophic factors. To identify novel factors that regulate human oligodendrocyte maturation/survival, we performed microarray analysis and identified genes expressed in moderate amounts in oligodendrocytes at 18–22 gestational weeks (gw). Among those characterized were the genes encoding the receptor tyrosine kinases, Axl and Mer. These receptors belong to the mammalian Axl/Mer/Rse receptor tyrosine kinase family and are developmentally regulated. The ligand for this family is the growth arrest‐specific 6 gene product (Gas6). Gas6 stimulates growth and prevents apoptosis in a variety of cell types. Oligodendrocytes isolated from 20 to 23 gw human fetal spinal cord were grown for 6 days on NIH 3T3 fibroblasts engineered to stably express Gas6 or on unmodified 3T3 cells. Oligodendrocytes were identified by immunostaining for proteins expressed by mature oligodendrocytes, CNPaseI and MBP. An increase in the numbers of CNPaseI+ and MBP+ oligodendrocytes, and the extent of process branching and extension, was observed when grown on irradiated 3T3‐cells secreting Gas6, but not on irradiated 3T3 cells. The effect of Gas6 was abolished in the presence of the Axl‐Fc receptor, but remained unchanged in the presence of TrkA‐Fc receptor. Our results suggest a role for the Gas6‐Axl signalling in regulating oligodendrocyte viability and maturation.