Basic Life Science Research Associate, Biology
Honors & Awards
Ruth Kirschstein National Research Service Award, National Institutes of Health (2012-2015)
National Science Foundation Graduate Research Fellowship, NSF (2004-2007)
Ph.D., University of California, San Francisco, Neuroscience (2010)
BS, University of Wisconsin-Madison, Zoology & Psychology (2001)
Polygenic sex determination in the cichlid fish Astatotilapia burtoni.
2016; 17 (1): 835-?
The East African riverine cichlid species Astatotilapia burtoni serves as an important laboratory model for sexually dimorphic physiology and behavior, and also serves as an outgroup species for the explosive adaptive radiations of cichlid species in Lake Malawi and Lake Victoria. An astounding diversity of genetic sex determination systems have been revealed within the adaptive radiation of East African cichlids thus far, including polygenic sex determination systems involving the epistatic interaction of multiple, independently segregating sex determination alleles. However, sex determination has remained unmapped in A. burtoni. Here we present mapping results supporting the presence of multiple, novel sex determination alleles, and thus the presence of polygenic sex determination in A. burtoni.Using mapping in small families in conjunction with restriction-site associated DNA sequencing strategies, we identify associations with sex at loci on linkage group 13 and linkage group 5-14. Inheritance patterns support an XY sex determination system on linkage group 5-14 (a chromosome fusion relative to other cichlids studied), and an XYW system on linkage group 13, and these associations are replicated in multiple families. Additionally, combining our genetic data with comparative genomic analysis identifies another fusion that is unassociated with sex, with linkage group 8-24 and linkage group 16-21 fused in A. burtoni relative to other East African cichlid species.We identify genetic signals supporting the presence of three previously unidentified sex determination alleles at two loci in the species A. burtoni, strongly supporting the presence of polygenic sex determination system in the species. These results provide a foundation for future mapping of multiple sex determination genes and their interactions. A better understanding of sex determination in A. burtoni provides important context for their use in behavioral studies, as well as studies of the evolution of genetic sex determination and sexual conflicts in East African cichlids.
View details for PubMedID 27784286
Dopaminergic inhibition of gonadotropin-releasing hormone neurons in the cichlid fish, Astatotilapia burtoni.
journal of experimental biology
Dopamine regulates reproduction in part by modulating neuronal activity within the hypothalamic-pituitary-gonadal (HPG) axis. Previous studies suggested numerous mechanisms by which dopamine exerts inhibitory control over the HPG axis, ultimately changing the levels of sex steroids that regulate reproductive behaviors. However, it is not known whether these mechanisms are conserved across vertebrate species. In particular, it is unknown whether mechanisms underlying dopaminergic control of reproduction are shared between mammals and teleost fish. In mammals, dopamine directly inhibits gonadotropin-releasing hormone (GnRH1) hypothalamic neurons, the gatekeepers for activation of the HPG axis. Here, we demonstrate, for the first time in teleost fish, dopaminergic control of GnRH1 neurons via direct dopamine type-2-like receptor (D2R)-mediated inhibition within the hypothalamus. These results suggest that direct dopaminergic control of GnRH1 neurons via interactions in the hypothalamus is not exclusive to tetrapod reproductive control, but is likely conserved across vertebrate species.
View details for PubMedID 27742893
Timing reproduction in teleost fish: cues and mechanisms
CURRENT OPINION IN NEUROBIOLOGY
2016; 38: 57-62
Fish comprise half of extant vertebrate species and use a rich variety of reproductive strategies that have yielded insights into the basic mechanisms that evolved for sex. To maximize the chances of fertilization and survival of offspring, fish species time reproduction to occur at optimal times. For years, ethologists have performed painstaking experiments to identify sensory inputs and behavioral outputs of the brain during mating. Here we review known mechanisms that generate sexual behavior, focusing on the factors that govern the timing of these displays. The development of new technologies, including high-throughput sequencing and genome engineering, has the potential to provide novel insights into how the vertebrate brain consummates mating at the appropriate time.
View details for DOI 10.1016/j.conb.2016.02.006
View details for Web of Science ID 000379556700010
View details for PubMedID 26952366
A Neural Basis for Control of Cichlid Female Reproductive Behavior by Prostaglandin F2a.
2016; 26 (7): 943-949
In most species, females time reproduction to coincide with fertility. Thus, identifying factors that signal fertility to the brain can provide access to neural circuits that control sexual behaviors. In vertebrates, levels of key signaling molecules rise at the time of fertility to prime the brain for reproductive behavior [1-11], but how and where they regulate neural circuits is not known [12, 13]. Specifically, 17α,20β-dihydroxyprogesterone (DHP) and prostaglandin F2α (PGF2α) levels rise in teleost fish around the time of ovulation [10, 14, 15]. In an African cichlid fish, Astatotilapia burtoni, fertile females select a mate and perform a stereotyped spawning routine, offering quantifiable behavioral outputs of neural circuits. We show that, within minutes, PGF2α injection activates a naturalistic pattern of sexual behavior in female A. burtoni. We also identify cells in the brain that transduce the prostaglandin signal to mate and show that the gonadal steroid DHP modulates mRNA levels of the putative receptor for PGF2α (Ptgfr). We use CRISPR/Cas9 to generate the first targeted gene mutation in A. burtoni and show that Ptgfr is necessary for the initiation of sexual behavior, uncoupling sexual behavior from reproductive status. Our findings are consistent with a model in which PGF2α communicates fertility status via Ptgfr to circuits in the brain that drive female sexual behavior. Our targeted genome modification in a cichlid fish shows that dissection of gene function can reveal basic control mechanisms for behaviors in this large family of species with diverse and fascinating social systems [16, 17].
View details for DOI 10.1016/j.cub.2016.01.067
View details for PubMedID 26996507
- A Neural Basis for Control of Cichlid Female Reproductive Behavior by Prostaglandin F-2 alpha CURRENT BIOLOGY 2016; 26 (7): 943-949
Electrical synapses connect a network of gonadotropin releasing hormone neurons in a cichlid fish
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
2015; 112 (12): 3805-3810
Initiating and regulating vertebrate reproduction requires pulsatile release of gonadotropin-releasing hormone (GnRH1) from the hypothalamus. Coordinated GnRH1 release, not simply elevated absolute levels, effects the release of pituitary gonadotropins that drive steroid production in the gonads. However, the mechanisms underlying synchronization of GnRH1 neurons are unknown. Control of synchronicity by gap junctions between GnRH1 neurons has been proposed but not previously found. We recorded simultaneously from pairs of transgenically labeled GnRH1 neurons in adult male Astatotilapia burtoni cichlid fish. We report that GnRH1 neurons are strongly and uniformly interconnected by electrical synapses that can drive spiking in connected cells and can be reversibly blocked by meclofenamic acid. Our results suggest that electrical synapses could promote coordinated spike firing in a cellular assemblage of GnRH1 neurons to produce the pulsatile output necessary for activation of the pituitary and reproduction.
View details for DOI 10.1073/pnas.1421851112
View details for Web of Science ID 000351477000061
View details for PubMedID 25775522
- Tol2-Mediated Generation of a Transgenic Haplochromine Cichlid, Astatotilapia burtoni PLOS ONE 2013; 8 (10)
Sexually Dimorphic Neurons in the Ventromedial Hypothalamus Govern Mating in Both Sexes and Aggression in Males
2013; 153 (4): 896-909
Sexual dimorphisms in the brain underlie behavioral sex differences, but the function of individual sexually dimorphic neuronal populations is poorly understood. Neuronal sexual dimorphisms typically represent quantitative differences in cell number, gene expression, or other features, and it is unknown whether these dimorphisms control sex-typical behavior exclusively in one sex or in both sexes. The progesterone receptor (PR) controls female sexual behavior, and we find many sex differences in number, distribution, or projections of PR-expressing neurons in the adult mouse brain. Using a genetic strategy we developed, we have ablated one such dimorphic PR-expressing neuronal population located in the ventromedial hypothalamus (VMH). Ablation of these neurons in females greatly diminishes sexual receptivity. Strikingly, the corresponding ablation in males reduces mating and aggression. Our findings reveal the functions of a molecularly defined, sexually dimorphic neuronal population in the brain. Moreover, we show that sexually dimorphic neurons can control distinct sex-typical behaviors in both sexes.
View details for DOI 10.1016/j.cell.2013.04.017
View details for Web of Science ID 000318844000017
View details for PubMedID 23663785
Tol2-mediated generation of a transgenic haplochromine cichlid, Astatotilapia burtoni.
2013; 8 (10)
Cichlid fishes represent one of the most species-rich and rapid radiations of a vertebrate family. These ∼2200 species, predominantly found in the East African Great Lakes, exhibit dramatic differences in anatomy, physiology, and behavior. However, the genetic bases for this radiation, and for the control of their divergent traits, are unknown. A flood of genomic and transcriptomic data promises to suggest mechanisms underlying the diversity, but transgenic technology will be needed to rigorously test the hypotheses generated. Here we demonstrate the successful use of the Tol2 transposon system to generate transgenic Astatotilapia burtoni, a haplochromine cichlid from Lake Tanganyika, carrying the GFP transgene under the control of the ubiquitous EF1α promoter. The transgene integrates into the genome, is successfully passed through the germline, and the widespread GFP expression pattern is stable across siblings and multiple generations. The stable inheritance and expression patterns indicate that the Tol2 system can be applied to generate A. burtoni transgenic lines. Transgenesis has proven to be a powerful technology for manipulating genes and cells in other model organisms and we anticipate that transgenic A. burtoni and other cichlids will be used to test the mechanisms underlying behavior and speciation.
View details for DOI 10.1371/journal.pone.0077647
View details for PubMedID 24204902
- The androgen receptor governs execution but not programming of male sexual and territorial behaviors NEURON 2010; 66: 260-272
A genetic approach to dissect sexually dimorphic behaviors
HORMONES AND BEHAVIOR
2008; 53 (5): 627-637
It has been known since antiquity that gender-specific behaviors are regulated by the gonads. We now know that testosterone is required for the appropriate display of male patterns of behavior. Estrogen and progesterone, on the other hand, are essential for female typical responses. Research from several groups also indicates that estrogen signaling is required for male typical behaviors. This finding raises the issue of the relative contribution of these two hormonal systems in the control of male typical behavioral displays. In this review we discuss the findings that led to these conclusions and suggest various genetic strategies that may be required to understand the relative roles of testosterone and estrogen signaling in the control of gender-specific behavior.
View details for DOI 10.1016/j.yhbeh.2007.12.012
View details for Web of Science ID 000256283100004
View details for PubMedID 18313055