Bruce S Baker

Howard Hughes Medical Institute | HHMI · Janelia Farm Research Campus

Animals execute one particular behavior among many others in a context-dependent manner, yet the mechanisms underlying such behavioral choice remain poorly understood. Here we studied how two fundamental behaviors, sex and sleep, interact at genetic and neuronal levels in Drosophila. We show that an increased need for sleep inhibits male sexual beh...

Significance Most sexually dimorphic features of Drosophila melanogaster are specified by the action of sex-specific transcription factors encoded by the doublesex ( dsx ) gene. Evolutionary changes in such sexually dimorphic features are often a result of changes in the cis -regulatory sequences of the DSX target genes. When a particular target ge...

Drosophila melanogaster females respond to male courtship by either rejecting the male or allowing copulation. The neural mechanisms underlying these female behaviors likely involve the integration of sensory information in the brain. Because doublesex (dsx) controls other aspects of female differentiation, we asked whether dsx-expressing neurons m...

During courtship, male Drosophila melanogaster sing a multipart courtship song to female flies. This song is of particular interest because (1) it is species specific and varies widely within the genus, (2) it is a gating stimulus for females, who are sensitive detectors of conspecific song, and (3) it is the only sexual signal that is under both n...

We show that a small subset of two to six subesophageal neurons, expressing the male products of the male courtship master regulator gene products fruitlessMale (fruM), are required in the early stages of the Drosophila melanogaster male courtship behavioral program. Loss of fruM expression or inhibition of synaptic transmission in these fruM(+) ne...

Wild-type D. melanogaster males innately possess the ability to perform a multistep courtship ritual to conspecific females. The potential for this behavior is specified by the male-specific products of the fruitless (fru(M)) gene; males without fru(M) do not court females when held in isolation. We show that such fru(M) null males acquire the pote...

Drosophila melanogaster adult males perform an elaborate courtship ritual to entice females to mate. fruitless (fru), a gene that is one of the key regulators of male courtship behavior, encodes multiple male-specific isoforms (FruM). These isoforms vary in their carboxy-terminal zinc finger domains, which are predicted to facilitate DNA binding. B...

Genetically hard-wired neural mechanisms must enforce behavioral reproductive isolation because interspecies courtship is rare even in sexually naïve animals of most species. We find that the chemoreceptor Gr32a inhibits male D. melanogaster from courting diverse fruit fly species. Gr32a recognizes nonvolatile aversive cues present on these reprodu...

Somatic sexual dimorphisms outside of the nervous system in Drosophila melanogaster are largely controlled by the male- and female-specific Doublesex transcription factors (DSX(M) and DSX(F), respectively). The DSX proteins must act at the right times and places in development to regulate the diverse array of genes that sculpt male and female chara...

DSX is present in the daughters of a recently divided SOP. Shown is DAPI staining of the ase-lacZ–expressing, anti-DSXDBD-stained cells from Fig. 4B. Two masses of DNA can be distinguished (green arrows), indicating separate nuclei. This pair of tightly associated cells expressing ase-lacZ is assumed to be the immediate daughters of a recently divi...

DSXM is not present in the male foreleg disc epithelium at 32 h 3I or preceding time points. (A–C) Male foreleg discs from the indicated time points of third instar larval development were stained for AC (left panels) and DSXM (middle panels). Right panels show merged images of DSXM (magenta), AC (green) and DAPI-stained DNA (blue). From 24–32 h 3I...

Some gustatory SOPs are dividing at 6 h APF. (A and B) T4–T2 region of male foreleg disc with poxn-GAL4 driving UAS-mCD8::GFP (green in middle and right panels) stained with DAPI (white in left panel, blue in middle and right panels) and 22C10 (red in right panel). (A) Several 22C10-positive cells expressing poxn-GAL4 have mitotic figures indicatin...

Sexual behaviors in animals are governed by inputs from multiple external sensory modalities. However, how these inputs are integrated to jointly control animal behavior is still poorly understood. Whereas visual information alone is not sufficient to induce courtship behavior in Drosophila melanogaster males, when a subset of male-specific fruitle...

Uncovering the direct regulatory targets of doublesex (dsx) and fruitless (fru) is crucial for an understanding of how they regulate sexual development, morphogenesis, differentiation and adult functions (including behavior) in Drosophila melanogaster. Using a modified DamID approach, we identified 650 DSX-binding regions in the genome from which w...

The male-specific Fruitless proteins (FruM) act to establish the potential for male courtship behavior in Drosophila melanogaster and are expressed in small groups of neurons throughout the nervous system. We screened ∼1000 GAL4 lines, using assays for general courtship, male-male interactions, and male fertility to determine the phenotypes resulti...

Abdomen bending and attempted copulation shown by a solitary UAS-dTrpA1/+ ; fruGAL4(B)/+ male at 29°C. (MOV)

A UAS-dTrpA1/+; fruGAL4(B)/+ male copulates with a wtcs female at 27°C. The female was introduced to the male after 5–10 min at 27°C when the male already showed wing extension and abdomen bending. (MOV)

Courtship behavior displayed by a solitary UAS-dTrpA1/+; dsxGAL4(Δ2)/+ male at 29°C. The male first showed wing extension (stage 1), and later abdomen bending (stage 2), then frequent attempted copulation and licking (stage 3). (MOV)

UAS-dTrpA1/+; dsxGAL4(Δ2)/+ male courtship in fruM+ and fruM− backgrounds. The first half of the movie shows a UAS-dTrpA1/+; dsxGAL4(Δ2)/+ male courting a headless female persistently at 27°C; while the second half shows a UAS-dTrpA1/+; dsxGAL4(Δ2), fruLexA/fru4–40 male displaying courtship behavior, but not to the headless female at 27°C. Headless...

Behavioral outputs of solitary males at 22°C, 25°C and 27°C for 15 min. Behaviors were scored for 15 min in solitary males with indicated genotypes after transfer from 22°C to 25°C or 27°C. No courtship-like behavior was observed at 22°C in all genotypes. Wing extension was induced at 25°C by activating all fruM but not dsx neurons; while abdomen b...

Behavioral outputs of solitary males at 29°C for 15 min. Behaviors were scored for 15 min in solitary males with indicated genotypes after transfer from 22°C to 29°C. No courtship-like behavior was observed at 29°C in solitary males with UAS-dTrpA1 or GAL4 (for either fruGAL4(D), fruGAL4(B), dsxGAL4(1) or dsxGAL4(Δ2)) alone. All solitary UAS-dTrpA1...

Comparison of expression patterns for dsxGAL4(1) and dsxGAL4(Δ2). Comparison of expression patterns generated by each of the two dsxGAL4 lines driving the UAS-mCD8::GFP membrane-bound GFP reporter. A comparison is shown only for tissues that were specifically examined in each dsxGAL4 line. “+” indicates expression was observed; “−” indicates expres...

Courtship behavior displayed by a solitary UAS-dTrpA1/+; fruGAL4(B)/+ male at 29°C. The male first showed wing extension (stage 1), and later other steps such as abdomen bending (stage 2), then frequent attempted copulation, licking and even ejaculation (stage 3), finally the male fell over and was on its back (stage 4). (MOV)

Courtship behavior displayed by a solitary UAS-dTrpA1/+; dsxGAL4(Δ2), fruLexA/fru4–40 male at 29°C. Wing extension and abdomen bending were elicited almost simultaneously. (MOV)

The innate sexual behaviors of Drosophila melanogaster males are an attractive system for elucidating how complex behavior patterns are generated. The potential for male sexual behavior in D. melanogaster is specified by the fruitless (fru) and doublesex (dsx) sex regulatory genes. We used the temperature-sensitive activator dTRPA1 to probe the rol...

dsxGAL4 is expressed in adult adipose tissue and oenocytes. (A) Expression of UAS-mCD8::GFP membrane-bound GFP reporter in a sheet of dorsal abdominal adipose cells from an adult male. Single confocal section shown. (B) Expression of UAS-RedStinger nuclear DsRed reporter reveals patches of oenocytes around the abdominal spiracles (arrows) of an adu...

dsxGAL4 is expressed in subsets of cells and tissues of adult digestive organs. Cross-sections and superficial views of various digestive organs from a 7-d-old adult female. DNA is stained with DAPI (blue in merge images). Confocal Z projections. (A) Expression of UAS-RedStinger nuclear DsRed reporter (dsx, red in merge) is seen in a subset of epit...

dsxGAL4 is expressed in genital and thoracic discs. (A) Expression of UAS-mCD8::GFP membrane-bound GFP reporter (green) in second instar larval tissue immunostained with anti-GFP. DNA is stained with DAPI (blue). A bilaterally symmetrical group of cells is revealed in the ventral posterior of the larva in the expected location of the genital disc....

dsxGAL4 is expressed in tissues associated with the genitalia of males and females. Expression of UAS-mCD8::GFP membrane-bound GFP reporter (green) and autofluorescence of cuticular elements (magenta) are shown for adult male (A–E) and female (F–J) samples. Confocal Z projections. (A) Seminal vesicle (bracket) and cross-section through ejaculatory...

View of whole 8-h APF forelegs shown in Fig. 2. Male (A) and female (B). The left panels show 22C10 staining, while the right panels are a merge of 22C10 (magenta), poxn-GAL4 driving UAS-mCD8::GFP (green), and DNA stained with DAPI (blue). Tarsal segments boundaries are indicated with light blue lines in left panels. Cells marked with 22C10 were cl...

The Drosophila melanogaster sex hierarchy controls sexual differentiation of somatic cells via the activities of the terminal genes in the hierarchy, doublesex (dsx) and fruitless (fru). We have targeted an insertion of GAL4 into the dsx gene, allowing us to visualize dsx-expressing cells in both sexes. Developmentally and as adults, we find that b...

Although nervous system sexual dimorphisms are known in many species, relatively little is understood about the molecular mechanisms generating these dimorphisms. Recent findings in Drosophila provide the tools for dissecting how neurogenesis and neuronal differentiation are modulated by the Drosophila sex-determination regulatory genes to produce...

Adult flies expressing ChR2 in muscle under the MHC-gs-GAL4 driver. Photostimulation results in robust muscle contraction, resulting in abdominal extension and protrusion. (0.30 MB MOV)

Adult flies expressing ChR2 in cholinergic neurons under cha-GAL4. Photostimulation results in a seizure-like response, which is dependent on supplementary ATR. (1.32 MB MOV)

Larvae expressing ChR2 in muscles under the control of twist-GAL4 and 24B-GAL4. Illumination causes paralysis in an ATR-dependent manner. (0.56 MB MOV)

Larvae expressing ChR2 in motor neurons with the D42-GAL4 driver show a full-body contraction upon illumination. (0.70 MB MOV)

Adult female flies expressing ChR2 under the acj6-GAL4 driver. Photostimulation induces a startle-like jump response, dependent on supplementary ATR. (2.72 MB MOV)

Background The genetic analysis of behavior in Drosophila melanogaster has linked genes controlling neuronal connectivity and physiology to specific neuronal circuits underlying a variety of innate behaviors. We investigated the circuitry underlying the adult startle response, using photoexcitation of neurons that produce the abnormal chemosensory...

Low stringency genomic library screens with genomic fragments from the sex determination gene doublesex identified the Drosophila secreted cuticle protein 73 (dsc73) gene, which encodes an 852-residue protein with an N-terminal signal sequence. In embryos, dsc73 RNA and protein are expressed to high levels in the epidermal cells that secrete the la...

Innate behaviors offer a unique opportunity to use genetic analysis to dissect and characterize the neural substrates of complex behavioral programs. Courtship in Drosophila involves a complex series of stereotyped behaviors that include numerous exchanges of multimodal sensory information over time. As we will discuss in this review, recent work h...

Robust innate behaviours are attractive systems for genetically dissecting how environmental cues are perceived and integrated to generate complex behaviours. During courtship, Drosophila males engage in a series of innate, stereotyped behaviours that are coordinated by specific sensory cues. However, little is known about the specific neural subst...

The adult structures of Drosophila melanogaster are derived from larval imaginal discs, which originate as clusters of cells within the embryonic ectoderm. The genital imaginal disc is composed of three primordia (female genital, male genital, and anal primordia) that originate from the embryonic tail segments A8, A9, and A10, respectively, and pro...

Bonus, a Drosophila TIF1 homolog, is a nuclear receptor cofactor required for viability, molting, and numerous morphological events. Here we establish a role for Bonus in the modulation of chromatin structure. We show that weak loss-of-function alleles of bonus have a more deleterious effect on males than on females. This male-enhanced lethality is...

In Drosophila melanogaster, somatic sexual differentiation is regulated by a well characterized genetic hierarchy, by which the ratio of X chromosomes to autosomes (X:A) ultimately directs the deployment of sex-specific transcription factors encoded by doublesex (dsx) and fruitless (fru). In other dipterans, the X:A ratio is not the primary sex-det...

It has been proposed that dosage compensation in Drosophila males occurs by binding of two core proteins, MSL-1 and MSL-2, to a set of 35-40 X chromosome "entry sites" that serve to nucleate mature complexes, termed compensasomes, which then spread to neighboring sequences to double expression of most X-linked genes. Here we show that any piece of...

Throughout the animal kingdom the innate nature of basic behaviour routines suggests that the underlying neuronal substrates necessary for their execution are genetically determined and developmentally programmed. Complex innate behaviours require proper timing and ordering of individual component behaviours. In Drosophila melanogaster, analyses of...

In virtually all animals, males and females are morphologically, physiologically and behaviorally distinct. Using cDNA microarrays representing one-third of Drosophila genes to identify genes expressed sex-differentially in somatic tissues, we performed an expression analysis on adult males and females that: (1) were wild type; (2) lacked a germlin...

The fruitless (fru) gene in Drosophila melanogaster is a multifunctional gene that has sex-specific functions in the regulation of male sexual behavior and sex-nonspecific functions affecting adult viability and external morphology. While much attention has focused on fru's sex-specific roles, less is known about its sex-nonspecific functions. We h...

Previous genetic studies indicated intersex (ix) functions only in females and that it acts near the end of the sex determination hierarchy to control somatic sexual differentiation in Drosophila melanogaster. We have cloned ix and characterized its function genetically, molecularly and biochemically. The ix pre-mRNA is not spliced, and ix mRNA is...

There has recently been a revolution in our understanding of how the Drosophila sex-determination hierarchy generates somatic sexual dimorphism. Most significantly, the sex hierarchy has been shown to modulate the activities of well-known signaling molecules (FGF, Wnt and TGF beta proteins) and transcription factors (BAB and DAC) to direct various...

Molecular genetic studies of Drosophila melanogaster have led to profound advances in understanding the regulation of development. Here we report gene expression patterns for nearly one-third of all Drosophila genes during a complete time course of development. Mutations that eliminate eye or germline tissue were used to further analyze tissue-spec...

A central issue in developmental biology is how the deployment of generic signaling proteins produces diverse specific outcomes. We show that Drosophila FGF is used, only in males, to recruit mesodermal cells expressing its receptor to become part of the genital imaginal disc. Male-specific deployment of FGF signaling is controlled by the sex deter...

Each Drosophila genital imaginal disc contains primordia for both male and female genitalia and analia. The sexually dimorphic development of this disc is governed by the sex-specific expression of doublesex (dsx). We present data that substantially revises our understanding of how dsx controls growth and differentiation in the genital disc. The cl...

A multibranched hierarchy of regulatory genes controls all aspects of somatic sexual development in Drosophila melanogaster. One branch of this hierarchy is headed by the fruitless (fru) gene and functions in the central nervous system, where it is necessary for male courtship behavior as well as the differentiation of a male-specific abdominal str...

The integration of multiple developmental cues is crucial to the combinatorial strategies for cell specification that underlie metazoan development. In the Drosophila genital imaginal disc, which gives rise to the sexually dimorphic genitalia and analia, sexual identity must be integrated with positional cues, in order to direct the appropriate sex...

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Dosage compensation is the process by which the expression levels of sex-linked genes are altered in one sex to offset a difference in sex-chromosome number between females and males of a heterogametic species. Degeneration of a sex-limited chromosome to produce heterogamety is a common, perhaps unavoidable, feature of sex-chromosome evolution. Sel...

Dosage compensation in Drosophila is mediated by genes known as "male-specific lethals" (msls). Several msls, including male-specific lethal-3 (msl-3), encode proteins of unknown function. We cloned the Drosophila virilis msl-3 gene. Using the information provided by the sequences of the Drosophila melanogaster and D. virilis genes, we found that s...

Recent advances in our understanding of dosage compensation in flies have centered on characterizing its sex-specificity, identifying the structural RNAs involved in the process, and determining how dosage compensation is targeted to particular sites on the X chromosome.

The fruitless (fru) gene functions in Drosophila males to establish the potential for male sexual behaviors. fru encodes a complex set of sex-specific and sex-nonspecific mRNAs through the use of multiple promoters and alternative pre-mRNA processing. The male-specific transcripts produced from the distal (P1) fru promoter are believed to be respon...

The rox1 and rox2 RNAs have been suggested to be components of the dosage compensation machinery in Drosophila. We show that both rox RNAs colocalize with the male-specific lethal proteins at hundreds of specific bands along the male X chromosome. The rox RNAs and MSL proteins also colocalize with the X chromosome in all somatic cells and are expre...

REVIEW There is substantial cytogenetic data indicating that the process of sex determination can evolve relatively rapidly. However, recent molecular studies on the evolution of the regulatory genes that control sex determination in the insect Drosophila melanogaster, the nematode Caenorhabditis elegans, and mammals suggest that, although certain...

REVIEW There is substantial cytogenetic data indicating that the process of sex determination can evolve relatively rapidly. However, recent molecular studies on the evolution of the regulatory genes that control sex determination in the insect Drosophila melanogaster , the nematode Caenorhabditis elegans , and mammals suggest that, although certa...

The hermaphrodite (her) gene is necessary for sexual differentiation in Drosophila. Our characterization of her's zygotic function suggests that one set of female-specific terminal differentiation genes, the yolk protein (yp) genes, is transcriptionally activated by two separate pathways. One is a female-specific pathway, which is positively regula...

The zygotic function of the hermaphrodite (her) gene of Drosophila plays an important role in sexual differentiation. Our molecular genetic characterization of her suggests that her is expressed sex non-specifically and independently of other known sex determination genes and that it acts together with the last genes in the sex determination hierar...

In Drosophila melanogaster, the fruitless (fru) gene controls essentially all aspects of male courtship behavior. It does this through sex-specific alternative splicing of the fru pre-mRNA, leading to the production of male-specific fru mRNAs capable of expressing male-specific fru proteins. Sex-specific fru splicing involves the choice between alt...

In Drosophila, dosage compensation occurs by increasing the transcription of the single male X chromosome. Four trans-acting factors encoded by the male-specific lethal genes are required for this process. Dosage compensation is restricted to males by the splicing regulator Sex-lethal, which functions to prevent the production of the MSL-2 protein...

Sex determination in Drosophila melanogaster is regulated by a cascade of splicing factors which direct the sex-specific expression of gene products needed for male and female differentiation. The splicing factor TRA-2 affects sex-specific splicing of multiple pre-mRNAs involved in sexual differentiation. The tra-2 gene itself expresses a complex s...

We have investigated the anterior and posterior compartmental organization of the genital imaginal disc. Unlike the thoracic discs, the genital disc is a compound disc consisting of three primordia--the female genital, male genital, and anal primordia. Here we provide evidence that each primordium is divided into anterior and posterior compartments...

The Drosophila splicing factor RBP1 participates together with TRA and TRA-2 in the regulation of alternative splicing of doublesex (dsx) pre-mRNA. It does so by recognizing RBP1 RNA target sequences in the dsx pre-mRNA. RBP1 belongs to the Ser-Arg-rich (SR) protein family of splicing factors, which have in common a N-terminal RNA recognition motif...

Sexual orientation and courtship behavior in Drosophila are regulated by fruitless (fru), the first gene in a branch of the sex-determination hierarchy functioning specifically in the central nervous system (CNS). The phenotypes of new fru mutants encompass nearly all aspects of male sexual behavior. Alternative splicing of fru transcripts produces...

In Drosophila equalization of the amounts of gene products produced by X-linked genes in the two sexes is achieved by hypertranscription of the single male X chromosome. This process, dosage compensation, is controlled by a set of male-specific lethal (msl) genes, that appear to act at the level of chromatin structure. The properties of the MSL pro...

In species where males and females differ in number of sex chromosomes, the expression of sex-linked genes is equalized by a process known as dosage compensation. In Drosophila melanogaster, dosage compensation is mediated by the binding of the products of the male-specific lethal (msl) genes to the single male X chromosome. Here we report that the...