During most of my career I have been interested in the developmental challenges of metamorphosis and the way that hormones orchestrate the underlying cellular and molecular events. In insects, molting and metamorphosis are regulated by two hormones: ecdysone, which causes molting and promotes metamorphosis, and juvenile hormone (JH), which allows larval molting but prevents metamorphosis. The insect epidermis makes the overlying cuticle or exoskeleton and in most insects is polymorphic, in that it must switch genetic programs at the time of metamorphosis to the pupa, then to the adult. Generation of the adult also depends on imaginal discs and primordia that grow during larval life, then differentiate when cued by the hormonal milieu at metamorphosis. Finally, larval-specific structures die at metamorphosis. Internally the central nervous system undergoes metamorphosis by a similar combination of remodeling of some neurons, development of new adult-specific neurons that were generated during larval growth, and cell death of larva-specific neurons.
Juvenile Hormone and Metamorphosis
Our previous studies on the epidermis of Lepidoptera showed that JH can prevent both the ecdysone-induced appearance of the transcription factor Broad that is necessary for specifying the pupal program and the ecdysone-induced disappearance of Broad that is necessary for the subsequent adult developmental program. In Drosophila, by contrast, JH does not prevent metamorphosis of the imaginal disc–derived structures but can prevent the adult differentiation of the imaginal abdominal epidermis derived from the histoblasts. In this case, JH treatment prevents the normal disappearance of Broad from the abdominal epidermis during adult differentiation, resulting in the formation of a pupal, rather than adult, cuticle.
The development of the optic lobe in Drosophila at the onset of metamorphosis is providing us a system in which to probe the cellular and molecular basis of JH action. JH is necessary for its normal prepupal development but must be absent during adult development to allow its normal differentiation. In this case, the role of JH is to prevent premature differentiation of the optic lobe in response to ecdysone before it has completed its normal growth phase, resulting in aberrant neuronal morphology and function. Conversely, excess JH at the onset of the prepupal period prevents the normal ingrowth of lamina and other neurons that form the adult visual circuits. The developmental defects in the optic lobe caused by the loss of JH are mimicked by the loss-of-function of the Methoprene-tolerant (Met) gene, which encodes a JH receptor, supporting its essential role in JH action. These studies are being conducted in collaboration with James Truman and Aljoscha Nern.
In Drosophila there are two related genes, Met and germ cell-expressed (gce), encoding the JH receptor. Using recombineered bacterial artificial chromosomes (BACs) for each, we are studying their tissue and developmental distribution in both the larva and the adult.
Hormones and Behavior
At the onset of metamorphosis, insect larvae cease feeding and begin wandering to find a pupation site. In Lepidoptera, this switch to wandering behavior is initiated by ecdysone acting in the absence of JH on the brain. Currently, I am exploring the neural circuitry underlying the ecdysone-induced change in phototactic behavior in Drosophila larvae at wandering.