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The nature of the sexes

One of the most fundamental processes in biology is the establishment of the male and female gender. Sex choice is generally determined by specific regulatory genes that form genetic cascades and control various aspects of sexual development, differentiation, physiology and behavior.

Sex-specific features are not restricted to the obvious anatomical differences between males and females and the distinct behaviors they display in social interactions, but extend into many other aspects in an animal's life history. For example, the two sexes are often differentially susceptible to disease, prefer different diets, have substantial differences in lifespan and might exhibit difference in non sex-specific behaviors such as foraging and circadian behavior.

Our laboratory uses the fruit fly, Drosophila melanogaster, to study the molecular underpinnings of sex-specific differences in higher animals. We are especially interested in elucidating the regulation and control of male- and female-specific mating behaviors. We are also trying to uncover the molecular basis for additional, well-known differences between the sexes, including the differences in lifespan (males have a significantly shorter lifespan than females) and circadian behavior.

An additional field of study is the complex process of dosage compensation, a universal process in species with sex chromosomes in order to assure balanced expression of X-linked genes. To identify sex-specific genes involved in these processes, we use various types of genomic analyses, such as Serial Analysis of Gene Expression (SAGE), genome database analyses and DNA micro arrays. Subsequent characterizations of identified genes include establishing detailed expression profiles and functional studies by RNA interference, gene knock-outs and ectopic expression.

Interpreting a complex external world

Whereas the two genders and their intimate interactions contribute to the survival of a species, recognizing and appropriately interpreting the complex external world and reacting to it with well-measured responses and behaviors is crucial for the survival of each individual.

In insects including Drosophila, a large part of the external world is represented in the form of hundreds, if not thousands, of distinct fragrances and odors recognized by sophisticated olfactory organs. Many such odor cues lead the fly to potential food sources, which are then further investigated - tasted - by a similarly sophisticated array of taste organs that include the labellum, legs and wings. Tasting potential foods allows animals to discern edible from contaminated foods, as well as foods with high caloric value from those with low caloric value.

We are interested in how flies distinguish between different food sources. An important step toward elucidating this question was the identification of the proteins that recognize various chemical substrates in the environment. These proteins are encoded by a large family of about 70 G-protein coupled receptor genes, generally referred to as gustatory (taste) receptor genes (Gr genes), and are expressed in sensory neurons present in all taste organs. Spatial segregation of at least some of the Gr genes provides a fundamental framework for taste discrimination.

To appropriately interpret what the individual GRs recognize, it is thought that the cells expressing specific GRs connected to defined regions of the taste centers in the brain. The ultimate goal of our studies is to elucidate how the peripheral sensory map is translated into a taste perception map in the brain.

To accomplish this, we employ numerous molecular genetic approaches, which allow us to visualize taste centers that receive specific taste sensory input. Moreover, these tools also enable us to 'shut off' the function of specific sets of taste cells (i.e. their input into the taste centers) and to investigate resulting changes in feeding behaviors.

"Tasting" the scent of a female

Our major interest in the study of sex-specific processes is currently focused on male courtship behavior, an innate behavior that is displayed exclusively by a male towards a female prior to copulation. The involvement of vision, chemoreception and audition offers ample opportunity to study this behavior from a variety of different angles.

Recently, we provided direct evidence for a sex-specific pheromone receptor gene involved during a specific sequence of the male courtship behavior. This gene, Gr68a, a member of the Gr gene family, is expressed in a single neuron of only about 10 male-specific pheromone bristles of each of the male's forelegs; we showed that these neurons are necessary to recognize pheromone cues from the female abdomen, cues that are mediate to the male brain during the "tapping step" of the courtship sequence. Moreover, we have knocked down expression of Gr68a by means of RNA interference and have found that Gr68a protein itself is required for "female recognition".

Our future interests are directed towards the identification of the female pheromones detected by GR68a, the role of additional Gr genes that might be involved in the same and/or additional micro-behaviors during male courtship and the broader context in which pheromone input is integrated with visual and auditory input.