Bone morphogenetic protein‐7 enhances dendritic growth and receptivity to innervation in cultured hippocampal neurons

Abstract

Members of the bone morphogenetic protein (BMP) family of growth factors are present in the central nervous system during development and throughout life. They are known to play an important regulatory role in cell differentiation, but their function in postmitotic telencephalic neurons has not been investigated. To address this question, we examined cultured hippocampal neurons following treatment with bone morphogenetic protein-7 (BMP-7, also referred to as osteogenic protein-1). When added at the time of plating, BMP-7 markedly stimulated the rate of dendritic development. Within 1 day, the dendritic length of BMP-7-treated neurons was more than twice that of controls. By three days the dendritic arbors of BMP-7-treated neurons had attained a level of branching similar to that of 2-week-old neurons cultured under standard conditions. Several findings indicate that BMP-7 selectively enhances dendritic development. While dendritic length was significantly increased in BMP-7-treated neurons, the length of the axon was not. In addition, the mRNA encoding the dendritic protein MAP2 was significantly increased by BMP-7 treatment, but the mRNA for tubulin was not. Finally, BMP-7 did not enhance cell survival. Because dendritic maturation is a rate-limiting step in synapse formation in hippocampal cultures, we examined whether BMP-7 accelerated the rate at which neurons became receptive to innervation. Using two separate experimental paradigms, we found that the rate of synapse formation (assessed by counting synapsin I-positive presynaptic vesicle clusters) was increased significantly in neurons that had been exposed previously to BMP-7. Because BMP-7 and related BMPs are expressed in the hippocampus in situ, these factors may play a role in regulating dendritic branching and synapse formation in both development and plasticity.

The Novel GTPase Rit Differentially Regulates Axonal and Dendritic Growth

“…BMP7 has previously been shown to enhance dendritic growth in cultured hippocampal neurons (Withers et al, 2000). Consistent with this observation, we observed that BMP7 (30 ng/ml for 3 d) significantly increased dendritic growth as evidenced by comparing the total length of the dendritic arbor in BMP7-treated (487 Ϯ 72 m) versus control (224 Ϯ 36 m) hippocampal cultures derived from the same dissection.…”

TGF-β Family Signaling in Neural and Neuronal Differentiation, Development, and Function

“…Strengthening synapses is necessary for learning and memory and for regenerating neuronal circuits after injury. BMP signaling regulates neurite outgrowth and dendritic development throughout the CNS, including cortical neurons Le Roux et al 1999;Lee-Hoeflich et al 2004;Podkowa et al 2010), hippocampal neurons (Withers et al 2000), and cerebellar neurons (Matsuura et al 2007). In culture, treatment of sympathetic neurons with BMP-2, BMP-5, BMP-6, or BMP-7 enhances dendritic development (Lein et al 1995(Lein et al , 1996Guo et al 1998;Beck et al 2001;Horbinski et al 2002).…”

The 3 Rs of Stroke Biology: Radial, Relayed, and Regenerative

“…The transforming growth factor (TGF) superfamily of cytokines contains several molecules that stimulate poststroke axonal sprouting. Bone morphogenic protein 7 stimulates dendritic growth in neurons and promotes behavioral recovery [34,35]. The TGF-β family member growth differentiation factor 10 (GDF10) is induced in peri-infarct cortex after stroke and is a potent stimulant for axonal sprouting and functional recovery [36].…”