Specification, differentiation, and maturation of the variety of cell types found in the developing central nervous system (CNS) requires interactions between internal molecular mechanisms and tightly controlled external signaling molecules. The Bone morphogenetic proteins (BMPs), which are expressed in dorsal spinal cord during embryogenesis, are involved in the specification of multiple CNS cell types, including roof plate and dorsal neurons, and have been implicated in glial development. There is mounting evidence that excess BMP signaling inhibits the differentiation of oligodendrocytes, the myelinating cells of the central nervous system, while promoting the development of astrocytes. However, the precise role of endogenous BMP signaling on gliogenesis is unclear.
I have investigated the role of BMP signaling in glial development in vitro and in vivo , in order to determine the effects of BMP on differentiated oligodendrocytes and to examine the role of endogenous BMP signaling in gliogenesis. Using purified cultures of immature oligodendrocytes, I have shown that BMP4 irreversibly inhibits myelin protein expression while increasing process extension. These results suggest that excess BMP signaling is inhibitory for oligodendrogenesis throughout the oligodendrocyte lineage. Using a genetic model in which signaling through type 1 BMP receptors is disrupted throughout the neural tube, I have shown that lack of BMP signaling results in fewer GFAP+ astrocytes in the spinal cord at P0, confirming that BMP signaling promotes astrocyte development. Surprisingly, Bmpr double mutant animals exhibit decreased numbers of mature oligodendrocytes, while the oligodendrocyte precursor population is unaffected, suggesting that endogenous BMPs may be directly or indirectly involved in promoting oligodendrocyte differentiation or maturation. These results provide new insights into the role of BMPs in glial development.
