Fig. 6.
Retrograde mechanisms in NMJ formation. (A) In Drosophila, muscle cells release TGFβ/Gbb for both post- and presynaptic assembly. Wnt released from presynaptic neurons activates the Frizzled-dependent pathway for presynaptic differentiation. (B) In rodents, muscle fibers release Gdnf, which activates the receptor tyrosine kinase Ret for presynaptic differentiation. FGF, synaptic laminin and synaptic collagens orchestrate the complex temporal control of presynaptic differentiation. The interaction of laminin β2 with P/Q type calcium channels might be required for nerve terminal maturation. Muscle fibers also regulate presynaptic differentiation via a pathway that requires muscle- but not motoneuron-generated β-catenin or β1 integrin.