Bone morphogenetic proteins (BMPs) regulate several aspects of neuronal behavior. For instance, BMP-2 has the ability to modulate, either positively or negatively, the outgrowth of neuronal processes in diverse cell types. In Drosophila motor neurons, the BMP type II receptor (BMPRII) homolog wishful thinking plays crucial roles on neuromuscular synaptogenesis signaling through Smad-dependent and Smad-independent pathways. However, a role for BMP signaling at the vertebrate neuromuscular junction has not been addressed. Herein, we have analyzed the expression of BMPRII and the effect of BMP-2 during the morphological differentiation of motor neuron-like NSC-34 cells. Our data indicate that BMPRII is up-regulated and becomes accumulated in somas and growth cones upon motor neuronal differentiation. BMP-2 inhibits the differentiation of NSC-34 cells, an effect that correlates with activation of a Smad-dependent pathway, induction of the inhibitory Id1 transcription factor, and down-regulation of the neurogenic factor Mash1. BMP-2 also activates effectors of Smad-independent pathways. Remarkably, BMP-2 treatment significantly increases the expression of BMPRII. Our findings provide the first evidence to suggest a role for BMP pathways on the differentiation of motor neurons leading to successful assembly and/or regeneration of the vertebrate neuromuscular synapse. Bone Morphogenetic Proteins (BMP) and their receptors regulate neuromuscular synaptogenesis in invertebrate species. Herein, we show that the differentiation of vertebrate motor neurons is accompanied by up-regulation of BMP receptor II (BMPRII) that becomes concentrated in growth cones. Remarkably, BMP-2 inhibits differentiation while it up-regulates BMPRII expression. Our findings suggest that BMP-2 inhibits axonal regeneration of motor neurons but, at the same time, it provides cells the required proteins, such as BMPRII, for proper synaptogenesis.
- motor neuron