Animals have evolved great diversity in innate behaviors. Evolutionary differences in behavior are often caused by functional or structural changes in the nervous system. In order to understand how behavior evolves, we must first understand how the nervous system develops and functions.
My research focuses on deciphering the neural mechanisms underlying the generation of innate behaviors in Drosophila that display variations across species. I plan to use what we learn about how the nervous system generates behavior as an entry into the problem of how the system changes during evolution. I am currently using courtship song in Drosophila as a model system.
My interest in the evolution of the nervous system and behavior has its roots in my graduate work, which I conducted with Mike McKeown at Brown University. In collaboration with Barbara Taylor (University of Oregon-Corvallis), I studied how sexually dimorphic courtship behaviors in Drosophila are genetically programmed. At the time, work from other groups had suggested a dichotomous model for the genetic control of sexually dimorphic traits in Drosophila, in which the doublesex gene (dsx) specified the soma, while the fruitless gene (fru) specified behavior. Our work demonstrated that complete control of Drosophila sexual behavior in fact results from genetic interactions between the dsx and fru genes, as well as with sex-non-specific pathways.
Early in graduate school, I began to wonder if the concepts that were emerging concerning the evolution of morphology would apply to behavior. I joined Sean Carroll's lab at University of Wisconsin-Madison in the spring of 2007 hoping that studying ‘Evo-Devo’ would set the stage for me to pursue how behavior and the nervous system evolve. The evolution of pheromone perception in Drosophila offered an opportunity to ask not only how behavior evolves, but also how chemical communication within and between closely related species may diverge. Pheromonal interactions can evolve by changes in either the production or perception of signals. I began my postdoc in the Carroll lab with the aim to investigate these and related issues.
My fellow postdoc Heloise Dufour and I found that certain differences in putative pheromone profiles in Drosophila have evolved in part by cis-regulatory changes in a pheromone-producing gene called desatF. We found that the desatF gene is directly regulated by DSX transcription factors, and that its female-specific expression evolved by the gain of a DSX binding site. Remarkably, we also discovered that in one species, monomorphic expression of desatF evolved from a dimorphic ancestor by a loss-of-function mutation in the DSX binding site.
As our work on the evolution of pheromone profiles came to a close, the lure and challenge of the nervous system and its evolution became irresistible for me. How do innate behaviors evolve? Are structural or physiological changes in the nervous system key? Where in the neural circuit that controls the behavior has evolution occurred? What kinds of genes and mutations contribute to behavioral evolution? I spent time searching for a simple place to build a foundation that will allow me to move toward these long-term questions.
‘Evo-Devo’ has shown that a firm understanding of developmental mechanisms is key in elucidating how morphology evolves. By analogy, the mechanisms governing the evolution of behavior will be illuminated only with a deep understanding of how nervous systems develop and function. Thus, in the spring of 2010, I joined Jim Truman's group at Janelia Farm to gain an expertise on the development of the nervous system, its assembly into circuits, and its control of behavior.
My present day research builds on my past efforts, but in an importantly new direction. Drosophila males court females in part by extending a wing and vibrating it to produce a species-specific “song.” Females use the song to decide if the courting male is an appropriate mating partner. Courtship songs are an ideal model system to study the evolution of behavior because they vary enormously among Drosophila species, and are experimentally tractable for phylogenetic studies and neurobiological and genetic dissection.
My approach to studying the evolution of courtship song is to begin with an understanding of its neural control in Drosophila melanogaster, then to use this information to pose testable hypotheses about its evolution in other Drosophila species.
The most systematic approach to dissect the neural control of Drosophila courtship song is to begin in the periphery with an understanding of the motor units that drive it. At JFRC, I have developed strategies to precisely dissect the function and anatomy of the motor pathways that control courtship song. This will give us insights into the neuromuscular mechanisms of song and provide a starting point to identify song-relevant neurons at deeper levels of the central nervous system. As our understanding of the song circuit unfolds, I plan to develop strategies to probe orthologous neurons in species with diverse song patterns and ask if their structure or function has evolved.
Prior Publications (5)
A wide range of organisms use sex pheromones to communicate with each other and to identify appropriate mating partners. While the evolution of chemical communication has been suggested to cause sexual isolation and speciation, the mechanisms that govern evolutionary transitions in sex pheromone production are poorly understood. Here, we decipher the molecular mechanisms underlying the rapid evolution in the expression of a gene involved in sex pheromone production in Drosophilid flies. Long-chain cuticular hydrocarbons (e.g., dienes) are produced female-specifically, notably via the activity of the desaturase DESAT-F, and are potent pheromones for male courtship behavior in Drosophila melanogaster. We show that across the genus Drosophila, the expression of this enzyme is correlated with long-chain diene production and has undergone an extraordinary number of evolutionary transitions, including six independent gene inactivations, three losses of expression without gene loss, and two transitions in sex-specificity. Furthermore, we show that evolutionary transitions from monomorphism to dimorphism (and its reversion) in desatF expression involved the gain (and the inactivation) of a binding-site for the sex-determination transcription factor, DOUBLESEX. In addition, we documented a surprising example of the gain of particular cis-regulatory motifs of the desatF locus via a set of small deletions. Together, our results suggest that frequent changes in the expression of pheromone-producing enzymes underlie evolutionary transitions in chemical communication, and reflect changing regimes of sexual selection, which may have contributed to speciation among Drosophila.
Sexual behavior in Drosophila results from interactions of multiple neural and genetic pathways. Male-specific fruitless (fruM) is a major component inducing male behaviors, but recent work indicates key roles for other sex-specific and sex-non-specific components. Notably, male-like courtship by retained (retn) mutant females reveals an intrinsic pathway for male behavior independent of fruM, while behavioral differences between males and females with equal levels of fruM expression indicate involvement of another sex-specific component. Indeed, sex-specific products of doublesex (dsxF and dsxM), that control sexual differentiation of the body, also contribute to sexual behavior and neural development of both sexes. In addition, the single product of the dissatisfaction (dsf) gene is needed for appropriate behavior in both sexes, implying additional complexities and levels of control. The genetic mechanisms controlling sexual behavior are similar to those controlling body sexual development, suggesting biological advantages of modifying an intermediate intrinsic pathway in generation of two substantially different behavioral or morphological states.
Current models describe male-specific fruitless (fruM) as a genetic 'switch' regulating sexual behavior in Drosophila melanogaster, and they postulate that female (F) and male (M) doublesex (dsx) products control body sexual morphology. In contradiction to this simple model, we show that dsx, as well as fruM and non-sex-specific retained (retn), affect both male and female sexual behaviors. In females, both retn and dsxF contribute to female receptivity, and both genes act to repress male-like courtship activity in the presence or absence of fruM. In males, consistent with the opposing functions of dsxM and dsxF, dsxM acts as a positive factor for male courtship. retn also acts counter to fruM in the development of the male-specific muscle of Lawrence. Molecularly, retn seems to regulate sexual behavior via a previously described complex that represses zerknullt. Thus, we show that fru and dsx together act as a 'switch' system regulating behavior in the context of other developmental genes, such as retn.
Drosophila retained/dead ringer is necessary for neuronal pathfinding, female receptivity and repression of fruitless independent male courtship behaviors.Development (Cambridge, England) 2005
L. M. Ditch, T. Shirangi, J. L. Pitman, K. L. Latham, K. D. Finley, P. T. Edeen, B. J. Taylor, and M. McKeown Development (Cambridge, England), 132:155-64 (2005)
Mutations in the Drosophila retained/dead ringer (retn) gene lead to female behavioral defects and alter a limited set of neurons in the CNS. retn is implicated as a major repressor of male courtship behavior in the absence of the fruitless (fru) male protein. retn females show fru-independent male-like courtship of males and females, and are highly resistant to courtship by males. Males mutant for retn court with normal parameters, although feminization of retn cells in males induces bisexuality. Alternatively spliced RNAs appear in the larval and pupal CNS, but none shows sex specificity. Post-embryonically, retn RNAs are expressed in a limited set of neurons in the CNS and eyes. Neural defects of retn mutant cells include mushroom body beta-lobe fusion and pathfinding errors by photoreceptor and subesophageal neurons. We posit that some of these retn-expressing cells function to repress a male behavioral pathway activated by fruM.
Nuclear degradation of p53 occurs during down-regulation of the p53 response after DNA damage.The FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology 2002
T. R. Shirangi, A. Zaika, and U. M. Moll The FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology, 16:420-2 (2002)
The principal regulator of p53 stability is HDM2, an E3 ligase that mediates p53 degradation via the ubiquitin-26S proteasome pathway. The current model holds that p53 degradation occurs exclusively on cytoplasmic proteasomes and hence has an absolute requirement for nuclear export of p53 via the CRM-1 pathway. However, proteasomes are abundant in both cytosol and nucleus, and no studies have been done to determine under what physiological circumstances p53 degradation might occur in the nucleus. We analyzed HDM2-mediated degradation of endogenous p53 in the presence of various nuclear export inhibitors of CRM-1, including leptomycin B (LMB), a noncompetitive, specific, and fast-acting inhibitor; and HTLV1-Rex protein, a potent competitive inhibitor. We found that significant HDM2-mediated p53 degradation took place in the presence of LMB or HTLV1-Rex, indicating that endogenous p53 degradation occurs locally in the nucleus, in parallel to cytoplasmic degradation. Moreover, p53 null cells that coexpressed export-defective mutants of p53 and HDM2 retained partial competence for p53 degradation. It is important that nuclear degradation of p53 occurred during the poststress recovery phase of a p53 response, after DNA damage ceased. We propose that the capability of local p53 degradation within the nucleus provides a tighter and faster control during the down-regulatory phase, when an active p53 program needs to be turned off quickly.