Look Ma, no cells. In what he calls “a hyper-low-tech experiment” by today's standards, Joshua Sanes was in 1978 able to show that regenerating nerve axons take their cues for new synapse formation from the extracellular matrix (ECM) of muscle cells and not from the cells themselves (Sanes et al., 1978). The beautiful simplicity of the experiment gave scientists studying synapse formation a clear trail to follow to find the signals for axon guidance and differentiation.
From the late 19th century studies by a student of Santiago Ramón y Cajal, it was known that a cut nerve would form a new synapse at the same exact spot on the muscle fiber where the old synapse had been.
“Somehow, the axon is ignoring 99.9% of the muscle fiber and contacting the 0.1%,” says Sanes. “It had to be recognizing something on that spot—a surface component or...
