Developmental Biology, Neuroscience
Janelia Research Campus
Dr. Riddiford is a senior fellow at the Janelia Research Campus.
Hormonal Control of Nervous System Development and Behavior
As a 16-year-old, Lynn Riddiford (née Moorhead) ran across a life-changing article while flipping through the pages of Seventeen magazine. Tucked amid all the fashion layouts and dating advice was an article about the summer research program at the Roscoe B. Jackson Memorial Laboratory in Bar Harbor, Maine. Intrigued, she wrote to the laboratory, requested an application, and set about convincing her parents to let her spend her summer 1,500 miles away from the farm she lived on in Illinois.
"It would have been the first year that I could have worked in the summer and it was going to cost them $15 a week," Riddiford remembers. Fortunately for Riddiford and the field of developmental biology, her parents agreed; her experiences at the Jackson Lab sparked a lifelong love of science. Most recently, that love has brought her to the Janelia Research Campus to explore further the role of hormones in development.
"Retiring to come to work in an environment like Janelia is a dream come true," Riddiford says. Janelia’s collaborative environment and outstanding research support services make for an unprecedented research opportunity, she says.
At Janelia, Riddiford will continue a focus on insect hormones that she began as an undergraduate at Radcliffe College, where she studied juvenile hormone—a hormone critical to molting and the development of insect larvae—in the laboratory of Carroll Williams.
"Juvenile hormone prevents metamorphosis in insects, so I rather foolishly asked Professor Williams if perhaps juvenile hormone played a role in tadpole development," Riddiford laughs. Her senior thesis proved it didn’t, but her fascination with the hormonal control of development stuck.
After detours to study newt limb regeneration and the physical chemistry of a muscle protein in graduate school at Cornell University, and of the enzyme human carbonic anhydrase as a postdoctoral fellow, Riddiford returned to the Williams laboratory in 1965 as a research fellow to study juvenile hormone and insect endocrinology. In 1966, she became the first female assistant professor in Harvard University’s biology department. "At the time, I couldn’t go into the main dining room of the faculty club because women weren’t permitted," she notes.
Riddiford focused on studying how juvenile hormone directed embryogenesis, molting, and metamorphosis, first in wild silkmoths, then in the tobacco hornworm (Manduca sexta). Her work at Harvard and, since 1973, at the University of Washington in Seattle has been instrumental in establishing the tobacco hornworm as the "laboratory rat" of insect endocrinology, particularly for studying the hormonal regulation of postembryonic development. While at Harvard, Riddiford also studied how hormones affected the sex behavior of wild silkmoth females, switching them from alluring virgins to motherly egg layers.
Focusing on juvenile hormone and its interaction with the insect steroid hormone ecdysone, Riddiford explored how these hormones affected isolated tissues. Early work demonstrated that ecdysone and related ecdysteroids could only trigger metamorphosis in the absence of juvenile hormone. "We know that juvenile hormone prevents metamorphosis," Riddiford says. "What we don’t know is how it prevents this switch."
She has some clues, however: juvenile hormone appears to interfere with a signal between ecdysteroids and a transcription factor encoded by the broad gene. Starting down the path toward metamorphosis requires the appearance of this transcription factor, which is prevented by juvenile hormone.
She and Janelia lab head James Truman, who was her first graduate student and is her husband of more than 35 years, recently unearthed a role for juvenile hormone independent from ecdysteroids: inhibiting the growth of imaginal discs—larval tissues destined to become adult eyes, wings, and legs—when inadequate food is available. A larva that experiences starvation at this critical time early in development becomes a smaller adult regardless of subsequent nutritional bounty.
"This finding moves us into the field of insulin," Riddiford says, noting that such effects have been described in the fruit fly Drosophila, but have been studied mostly as a function of insulin-like peptides. The work by Riddiford and her students has demonstrated that the insulin-like peptides that signal starvation during early growth of these imaginal discs work together with nutrition-independent growth controls from juvenile hormone to have profound effects on adult size.
Riddiford is looking forward to the opportunities to work with other Janelia investigators to see how her recent findings on hormonal control are related to other aspects of development, especially nervous system development.