Moreover reduction of syt was shown to substantially alter synaptic function at larval NMJs, with decreased neurotransmitter release, smaller evoked synaptic potentials and detectable morphological changes in the arborization of the synapse. BMP signaling is a highly conserved pathway that is essential for organized assembly of synapses and is critical for coordinated growth of neurons during development in both invertebrates and vertebrates. In the Drosophila NMJ, BMP retrograde signaling is required for synaptic terminal growth and functional refinement. The muscle derived BMP ligand, Gbb, signals through neuronal receptors wit, tkv and sax. Receptor activation then leads to an increase in the phosphorylation of RSmad, mad, at the NMJ terminals followed by nuclear translocation of p-Mad through its interaction with the GDC-0199 co-Smad, med. Mutations of the members of this cascade show drastic reduction in the number of synaptic boutons and in the amount of neurotransmitter release at the NMJs, including axonal transport defects. However, although the neuronal derived BMP ligands and receptors are expressed in multiple cells in the CNS and they function at the NMJs, the mechanism by which the retrograde signal is translocated into the nucleus has not yet been fully identified. There are at least two possible mechanisms by which BMP signals move retrogradely. One possibility is that similar to the NGF-TrkA signaling endosome, components of the BMP pathway are trafficked within the axon in a signaling endosome. Studies have shown that BMP receptors colocalize with each other and with endosomal markers. wit and tkv tagged GFP vesicles move bi-directionally within axons, however Mad tagged GFP appeared cytoplasmic, and axonal blockages were observed with loss of function of tkv, mad, sax, and wit. Yeast two hybrid analysis and binding assays identified that Tctex-1, the regulatory light chain of dynein binds BMPR-II, the mammalian wit orthologue. Consistent with these results, our analysis showed that neuronal derived BMP receptors and ligands functionally interact with both kinesin-1 and dynein motors indicating that these components can be transported within the axon via an association with molecular motors. Normally p-Mad localization is observed in motor neuron cell bodies, axons and NMJs, and disruption of the dynein complex by either loss of roblk or excess of DN Glued perturbed BMP signaling, as measured by p-Mad. Further, a direct link between the activation of BMP signaling and the growth of presynaptic arbors has also been identified. Ball et al demonstrated that Trio, the Rho-type guanyl-nucleotide exchange factor is under the transcriptional control of BMP signaling and, together with Rac, is involved in presynaptic growth and regulation of neurotransmitter release. In addition, loss of function of BMP components or motor proteins drastically reduced the number of synaptic boutons and the amount of neurotransmitter release.