The recognition of specific DNA-binding sites by transcription factors is a critical yet poorly understood step in the control of gene expression. Members of the Hox family of transcription factors bind DNA by making nearly identical major groove contacts via the recognition helices of their homeodomains. In vivo specificity, however, often depends on extended and unstructured regions that link Hox homeodomains to a DNA-bound cofactor, Extradenticle (Exd). Using a combination of structure determination, computational analysis, and in vitro and in vivo assays, we show that Hox proteins recognize specific Hox-Exd binding sites via residues located in these extended regions that insert into the minor groove but only when presented with the correct DNA sequence. Our results suggest that these residues, which are conserved in a paralog-specific manner, confer specificity by recognizing a sequence-dependent DNA structure instead of directly reading a specific DNA sequence.

We develop a new system for studying how innate drives are tuned to reflect current physiological needs and capacities, and how they affect sensory-motor processing. We demonstrate the existence of male mating drive in Drosophila, which is transiently and cumulatively reduced as reproductive capacity is depleted by copulations. Dopaminergic activity in the anterior of the superior medial protocerebrum (SMPa) is also transiently and cumulatively reduced in response to matings and serves as a functional neuronal correlate of mating drive. The dopamine signal is transmitted through the D1-like DopR2 receptor to P1 neurons, which also integrate sensory information relevant to the perception of females, and which project to courtship motor centers that initiate and maintain courtship behavior. Mating drive therefore converges with sensory information from the female at the point of transition to motor output, controlling the propensity of a sensory percept to trigger goal-directed behavior.

Selector genes modify developmental pathways to sculpt animal body parts. Although body parts differ in size, the ways in which selector genes create size differences are unknown. We have studied how the Drosophila Hox gene Ultrabithorax (Ubx) limits the size of the haltere, which, by the end of larval development, has ∼fivefold fewer cells than the wing. We find that Ubx controls haltere size by restricting both the transcription and the mobility of the morphogen Decapentaplegic (Dpp). Ubx restricts Dpp's distribution in the haltere by increasing the amounts of the Dpp receptor, thickveins. Because morphogens control tissue growth in many contexts, these findings provide a potentially general mechanism for how selector genes modify organ sizes.Changes in body part sizes have been critical for diversification and specialization of animal species during evolution. The beaks of Darwin's finches provide a famous example for how adaptation can produce variations in size and shape that allowed these birds to take advantage of specialized ecological niches and food supplies (1). Sizes also vary between homologous structures within an individual. For example, vertebrate digits and ribs vary in size, likely due to the activities of selector genes such as the Hox genes (2-4). Although the control of organ growth by selector genes is likely to be common in animal development (2,5,6), little is known about the mechanisms underlying this control.The two flight appendages of Drosophila melanogaster, the wing and the haltere, provide a classic example of serially homologous structures of different sizes (Fig. 1A). Halteres, appendages used for balance during flight, are thought to have been modified from full-sized hindwings during the evolution of two-winged flies from their four-winged ancestors (7,8). All aspects of haltere development that distinguish it from a wing, including its reduced size, are under the control of the Hox gene Ultra-bithorax (Ubx),which is expressed in all haltere imaginal disc cells but not in wing imaginal disc cells (8,9) (Fig. 1B). At all stages of development, haltere and wing primordia (imaginal discs) are different sizes. In the embryo, the wing primordium has about twice as many cells as the haltere primordium (7,10). By the end of larval development, the wing disc has ∼five times more cells (∼50,000) than the haltere disc (∼10,000) (11) [Fig. 1B and Supporting Online Material (SOM) Text]. The wing and haltere appendages will form from the pouch region of these mature discs ( fig. S1). The final step that contributes to wing and haltere size differences occurs during metamorphosis, when wing, but not haltere, cells flatten, thus increasing the surface area of the final appendage (12). fig. S1, and SOM Text). Compared with the wing, the stripe of dpp expression in the haltere was reduced in both its width and intensity, as reported by a lacZ insertion into the dpp locus (dpp-lacZ). There was also a difference in the profile of Dpp pathway activation, as visualized by an antibody that...

Behavioral persistence is a major factor in determining when and under which circumstances animals will terminate their current activity and transition into more profitable, appropriate, or urgent behavior. We show that, for the first 5 min of copulation in Drosophila, stressful stimuli do not interrupt mating, whereas 10 min later, even minor perturbations are sufficient to terminate copulation. This decline in persistence occurs as the probability of successful mating increases and is promoted by approximately eight sexually dimorphic, GABAergic interneurons of the male abdominal ganglion. When these interneurons were silenced, persistence increased and males copulated far longer than required for successful mating. When these interneurons were stimulated, persistence decreased and copulations were shortened. In contrast, dopaminergic neurons of the ventral nerve cord promote copulation persistence and extend copulation duration. Thus, copulation duration in Drosophila is a product of gradually declining persistence controlled by opposing neuronal populations using conserved neurotransmission systems.