James W. Truman

While still in graduate school at Harvard, Truman identified an insect neurohormone now known as the eclosion hormone, which mediates moth ecdysis.[1] He demonstrated that injecting eclosion hormone (EH) into moths elicits a stereotyped sequence of ecdysis behaviors.[3] In future studies of silkmoth eclosion, Truman went on to confirm the role of EH in mediating ecdysis. Later studies also implicated a brain-based circadian clock as the regulator controlling the release of EH.

As a junior fellow in the Harvard Society of Fellows,[1] Truman studied the underlying mechanisms of silkmoth eclosion, mainly focusing on the role of the circadian clock in driving time of day rhythms in eclosion. Truman demonstrated that eclosion rhythms persist in Hyalophora cecropia moths that have had their compound eyes, corpora cardiaca, and corpora allata surgically removed.[4] Eclosion rhythms were only abolished with the removal of the brain, indicating that the circadian clock is located within the brain.[4] Further experiments involving brain transplantation and selective illumination of different parts of the body revealed that the circadian photoreceptors, which are responsible for receiving light information to entrain the circadian clock, are also located in the brain.

More brain transplant experiments in Hyalophora cecropia and Antheraea pernyi showed that both entrained and free-running eclosion rhythms can be rescued in debrained moths that have had brains transplanted into their abdomens.[4] These restored eclosion rhythms in the debrained moths matched in phase angle with the eclosion rhythms observed in the donor moths prior to brain transplantation. These results confirmed Truman's previous findings that the circadian clock is located within the brain and that the factor mediating eclosion behavior is hormonal. Similar experiments focusing on the role of the circadian clock in regulating flight rhythms confirmed that extraretinal photoreceptors in the brain are responsible for entraining a brain-based circadian clock.[5]

In 2008, Truman went on to discover that eclosion rhythms, which are mediated by the circadian release of the neurohormone EH, can be masked.[6] In chronobiology, masking refers to the apparent coupling of an observable biological rhythm with an external environmental time cue, without affecting the underlying circadian clock that mediates the observed rhythm. Truman and colleagues observed increased eclosion in adult Drosophila flies immediately following a lights-on signal, which lead to their subsequent discovery that light triggers rapid eclosion in Drosophila on the condition that there was prior EH release. This occurs through the convergence of parallel neurosecretory pathways, both of which are activated by EH. These two EH activated pathways oppose each other; one is an excitatory behavioral pathway and one is inhibitory. Truman and colleagues found that the presence of light can result in the inhibition of the inhibitory pathway, leading to a greater net effect of the excitatory pathway. This light-mediated response promotes more rapid Drosophila eclosion and as a result masks the circadian eclosion rhythms. Further work with Drosophila resulted in the finding that masking of circadian eclosion rhythms can also occur through the inhibition of eclosion. In 2008, Truman and colleagues found that expression of the light chain of tetanus toxin (UAS-TNT) can affect the release of EH from EH releasing cells in the fly brain.[7] This inhibition of EH release results in the inhibition of eclosion—pointing to another way to mask circadian eclosion in Drosophila.

Some of Truman's most influential work outside of chronobiology involves how hormones alter the nervous system to influence behavior in insect models. Notably, Truman and colleagues have studied neuronal remodeling during insect metamorphosis. Their model organism, the hornworm moth (Manduca sexta), was chosen because it has a well-studied endocrinology and its large size allows for the use of standard electrophysiological and neuroanatomical techniques.[8] In 1986, Truman found that accompanying the bodily changes of the hornworm moth was an extensive reorganization of the moth's central nervous system (CNS). Among many changes was the finding that upon onset of metamorphosis, vast cell death sweeps through nests of larvae that are at the end of larval life. These nest cells were previously in an arrested state, but after this metamorphosis-induced cell death, the surviving nest cells can then differentiate. These cells become functional adult CNS neurons.

Following his interest in the evolution of metamorphosis, Truman began conducting research on the evolution of the insect nervous system at the Janelia Research Campus. Working in Drosophila model systems, he corroborated his findings from his work in Manduca sexta and discovered that as the adult insect CNS develops during metamorphosis, neuronal stem cells (neuroblasts) differentiate based on specific, highly conserved lineages. He also identified that the peripheral nervous system and motor neurons develop during the embryonic stage and are only partially remodeled during metamorphosis.[9] Furthermore, Truman and his colleagues identified that neuroblasts in the ventral nerve cord originate specific neuronal lineages extending to different regions of the insect body, and that these neuroblasts are characterized by position, size, and manner in which they divide.[10] Currently, Truman and his colleagues at the University of Washington are focusing on characterizing these neuronal lineages in the Drosophila CNS.