O'Connor and his colleagues were not specifically searching for genes involved in synaptic development when they began their screen of the Drosophila genome. Rather, they were looking for new members of the "bone morphogenetic protein" (BMP) receptor family. BMPs have previously been implicated in mediating many different aspects of development.
"Before we began the search, we didn't know that there was any BMP signaling in neurons," said O'Connor. "It has been known for some time that BMPs can affect neuronal cell fate, but that's very different from synaptic growth. So, we set out to identify genes for receptors, isolate mutants and just go where the resulting phenotypes took us."
Taking a different approach, Goodman and his colleagues at the University of California, Berkeley, did a direct screen for mutations in Drosophila genes that affect synaptic growth in Drosophila larvae. According to Goodman, synaptic growth likely involves proteins on either side of the synapse between neurons and muscle cells -- that is, the transmitting "presynaptic" side on the neuron and the receiving "postsynaptic" side on the muscle cell.
"From many experiments we had done over the past five years, we had accumulated evidence that the two sides of the synapse had a complex conversation with each other to regulate size and strength," said Goodman, who is now President and Chief Executive Officer at Renovis, Inc., a biotechnology company in San Francisco. "The genetic evidence clearly suggested the existence of several different retrograde factors -- signaling molecules that originated from the postsynaptic side of the synapse that influenced the growth or amount of transmitter release by the presynaptic side."
Researchers in Goodmans laboratory mounted a large-scale effort to create fly mutants that exhibited abnormalities in various parts of the synaptic machinery, which they detected using microsco
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Contact: Jim Keeley
keeleyj@hhmi.org
301-215-8858
Howard Hughes Medical Institute
14-Feb-2002