Telling Front From Back: Understanding Signaling Molecules Unlock Development

To unlock understanding about human development, Michael O’Connor is starting small.

O’Connor chose the fruit fly as a model to study questions of developmental biology. Fruit flies have advantages of rapid reproduction and low cost. More importantly, scientists can easily cause mutations in the fruit fly.

The implications from this tiny insect can be huge for human development, says O’Connor, a Howard Hughes Medical Institute Investigator at the University of Minnesota, because many of the genes’ action in the fruit fly are the same in humans “but it is much easier to study gene function in flies,” he says.

Whether fruit fly or human, creatures develop from a single cell into multi-celled organisms with many specialized tissues. To accomplish this, the organism’s cells have to communicate with each other about spatial relationships: How do they distinguish their front from their back? (Or their dorsal from their ventral sides, to use scientists’ lingo?)

He and his laboratory staff look for mutant genes that affect fruit flies’ front and back specification. Then, they investigate whether these genes are the same in vertebrates, including humans. If they are, then their discoveries of basic, genetic and molecular processes in fruit flies have implications for human development and health.

For example, O’Connor found that the molecular signaling process that helps an organism to specify its front from its back is activated again later in the development of neuronal synapses which conduct information between nerve cells and ultimately are critical for learning and memory.

Understanding these same signaling pathways may also have implications for cancer treatment: Cancer tumors cannot thrive without new blood vessels and the signaling mechanisms O’Connor studies affects blood vessel development. If those signals could be cut off, tumors could be starved for nutrients.

Developmental timing is another intriguing question, says O’Connor, father to two teenage boys. “How does the body know it’s ready for sexual maturity?” Insects demonstrate striking transitions, shedding exoskeletons periodically or morphing from a maggot into a fruit fly. The steroid hormone that triggers that transition is similar to estrogen and androgen. What triggers the release of this hormone at certain periods is not known, he says.

If scientists can identify what signals the timing of hormone production and so can learn to interfere with normal development, they might prevent larvae from becoming mosquitoes. By targeting these processes, researchers could create new families of ecologically responsible pesticides. Perhaps, O’Connor adds, we could target a pesticide that stymies mosquitoes from growing up yet protects butterflies.

“We have an eye out for how these discoveries might affect everyday life.”