'Wishful thinking' gene regulates neural d...( pic examination. The two research t...)

The two research teams found one BMP receptor gene -- which they dubbed wishful thinking -- that seemed to be involved in synaptic growth and development.

"The first hint that wit probably had a neuronal aspect to its function came when we looked at the expression pattern for the receptor and found it to be heavily expressed in the nervous system," said OConnor. Other researchers had already screened the chromosomal region containing wit for mutations, and O'Connor and his colleagues identified fly mutations in which wit function was eliminated. Although the mutant flies died before they emerged from their pupal case, initial examination of those flies revealed no obvious abnormalities. At that point, the researchers believed it was only wishful thinking to hope for a more dramatic effect of the mutation -- hence the genes name, said OConnor. But when lead author of the Neuron paper, Guillermo Marques, studied the mutants more closely, he discovered something surprising.

"Guillermo saw that the flies were moving inside the pupal case, but they couldn't get out -- and if he pulled them out, they had very spastic movements. This suggested to us that they had a neuronal defect of some sort but the animals' nerve cells appeared normal," said OConnor.

Two of OConnors co-authors, Bing Zhang and Hong Bao of the University of Texas, Austin, discovered that even though the general architecture of the mutant flies' nervous systems appeared normal, these animals exhibited severe defects in synaptic transmission. Their additional studies revealed that the mutants were also defective in releasing neurotransmitters from tiny sacs called synaptic vesicles. Examination of the synapses of the mutant flies' neurons also revealed that they had fewer synaptic "boutons" -- the small bulbs from which the neuron sends signals to the muscle cell.

O'Connor and his colleagues also began to trace
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Contact: Jim Keeley
keeleyj@hhmi.org
301-215-8858
Howard Hughes Medical Institute
14-Feb-2002