Papers by Russell Fernald
Background: Cichlid fishes have evolved remarkably diverse reproductive, social, and feeding beha... more Background: Cichlid fishes have evolved remarkably diverse reproductive, social, and feeding behaviors. Cell-to-cell signaling molecules, notably neuropeptides and peptide hormones, are known to regulate these behaviors across vertebrates. This class of signaling molecules derives from prohormone genes that have undergone multiple duplications and losses in fishes. Whether and how subfunctionalization, neofunctionalization, or losses of neuropeptides and peptide hormones have contributed to fish behavioral diversity is largely unknown. Information on fish prohormones has been limited and is complicated by the whole genome duplication of the teleost ancestor. We combined bioinformatics, mass spectrometry-enabled peptidomics, and molecular techniques to identify the suite of neuropeptide prohormones and pituitary peptide products in Astatotilapia burtoni, a well-studied member of the diverse African cichlid clade. Results: Utilizing the A. burtoni genome, we identified 148 prohormone genes, with 21 identified as a single copy and 39 with at least 2 duplicated copies. Retention of prohormone duplicates was therefore 41 %, which is markedly above previous reports for the genome-wide average in teleosts. Beyond the expected whole genome duplication, differences between cichlids and mammals can be attributed to gene loss in tetrapods and additional duplication after divergence. Mass spectrometric analysis of the pituitary identified 620 unique peptide sequences that were matched to 120 unique proteins. Finally, we used in situ hybridization to localize the expression of galanin, a prohormone with exceptional sequence divergence in cichlids, as well as the expression of a proopiomelanocortin, prohormone that has undergone an additional duplication in some bony fish lineages. Conclusion: We characterized the A. burtoni prohormone complement. Two thirds of prohormone families contain duplications either from the teleost whole genome duplication or a more recent duplication. Our bioinformatic and mass spectrometric findings provide information on a major vertebrate clade that will further our understanding of the functional ramifications of these prohormone losses, duplications, and sequence changes across vertebrate evolution. In the context of the cichlid radiation, these findings will also facilitate the exploration of neuropeptide and peptide hormone function in behavioral diversity both within A. burtoni and across cichlid and other fish species.
In vertebrates, circulating androgen levels are regulated by the hypothalamic-pituitary-gonadal (... more In vertebrates, circulating androgen levels are regulated by the hypothalamic-pituitary-gonadal (HPG) axis through which the brain controls the gonads via the pituitary. Androgen levels ultimately depend on factors including season, temperature, social circumstance, age, and other variables related to reproductive capacity and opportunity. Previous studies with an African cichlid fish, Astatotilapia burtoni, suggested that changes in both testosterone and 11-ketotestosterone
The Journal of neuroscience : the official journal of the Society for Neuroscience, Jan 15, 2000
Many animal species show flexible behavioral responses to environmental and social changes. Such ... more Many animal species show flexible behavioral responses to environmental and social changes. Such responses typically require changes in the neural substrate responsible for particular behavioral states. We have shown previously in the African cichlid fish, Haplochromis burtoni, that changes in social status, including events such as losing or winning a territorial encounter, result in changes in somatic growth rate. Here we demonstrate for the first time that changes in social status cause changes in the size of neurons involved in the control of growth. Specifically, somatostatin-containing neurons in the hypothalamus of H. burtoni increase up to threefold in volume in dominant and socially descending animals compared with cell sizes in subordinate and socially ascending fish. Because somatostatin is known to be an inhibitor of growth hormone release, the differences in cell size suggest a possible mechanism to account for the more rapid growth rates of subordinate and socially asc...
The Journal of neuroscience : the official journal of the Society for Neuroscience, Jan 15, 1997
Many aspects of reproductive physiology are subject to regulation by social interactions. These i... more Many aspects of reproductive physiology are subject to regulation by social interactions. These include changes in neural and physiological substrates of reproduction. How can social behavior produce such changes? In experiments reported here, we manipulated the social settings of teleost fish and measured the effect (1) on stress response as reflected in cortisol production, (2) on reproductive potential as measured in production of the signaling peptide, gonadotropin-releasing hormone, and (3) on reproductive function measured in gonad size. Our results reveal that the level of the stress hormone cortisol depends critically on both the social and reproductive status of an individual fish and on the stability of its social situation. Moreover, the reproductive capacity of an individual fish depends on these same variables. These results show that social encounters within particular social contexts have a profound effect on the stress levels as well as on reproductive competence. So...
Integrative and comparative biology, 2014
An organism's ability to adapt to its environment depends on its ability to regulate and main... more An organism's ability to adapt to its environment depends on its ability to regulate and maintain tissue specific, temporal patterns of gene transcription in response to specific environmental cues. Epigenetic mechanisms are responsible for many of the intricacies of a gene's regulation that alter expression patterns without affecting the genetic sequence. In particular, DNA methylation has been shown to have an important role in regulating early development and in some human diseases. Within these domains, DNA methylation has been extensively characterized over the past 60 years, but the discovery of its role in regulating behavioral outcomes has led to renewed interest in its potential roles in animal behavior and phenotypic plasticity. The conservation of DNA methylation across the animal kingdom suggests a possible role in the plasticity of genomic responses to environmental cues in natural environments. Here, we review the historical context for the study of DNA methyla...
Proceedings of the National Academy of Sciences of the United States of America, 1999
The life-history strategies of organisms are sculpted over evolutionary time by the relative pros... more The life-history strategies of organisms are sculpted over evolutionary time by the relative prospects of present and future reproductive success. As a consequence, animals of many species show flexible behavioral responses to environmental and social change. Here we show that disruption of the habitat of a colony of African cichlid fish, Haplochromis burtoni (Gü nther) caused males to switch social status more frequently than animals kept in a stable environment. H. burtoni males can be either reproductively active, guarding a territory, or reproductively inactive (nonterritorial). Although on average 25-50% of the males are territorial in both the stable and unstable environments, during the 20-week study, nearly two-thirds of the animals became territorial for at least 1 week. Moreover, many fish changed social status several times. Surprisingly, the induced changes in social status caused changes in somatic growth. Nonterritorial males and animals ascending in social rank showed an increased growth rate whereas territorial males and animals descending in social rank slowed their growth rate or even shrank. Similar behavioral and physiological changes are caused by social change in animals kept in stable environmental conditions, although at a lower rate. This suggests that differential growth, in interaction with environmental conditions, is a central mechanism underlying the changes in social status. Such reversible phenotypic plasticity in a crucial life-history trait may have evolved to enable animals to shift resources from reproduction to growth or vice versa, depending on present and future reproductive prospects.
Variation in reproductive capacity is common across the lives of all animals. In vertebrates, hyp... more Variation in reproductive capacity is common across the lives of all animals. In vertebrates, hypothalamic neurons that secrete GnRH are a primary mediator of such reproductive plasticity. Since social interactions suppress gonadal maturity in the Afri- can cichlid fish, Astatotilapia (Haplochromis) burtoni, we inves- tigated whether the electrical properties of GnRH neurons were also socially regulated. Adult A. burtoni males are either terri- torial (T) and reproductively active or nonterritorial (NT) and reproductively regressed, depending upon their social environ- ment. We compared the basic electrical properties of hypotha- lamic GnRH neurons from T and NT males using whole-cell elec- trophysiology in vitro. GnRH neurons were spontaneously active and exhibited several different activity patterns. A small fraction of neurons exhibited episodic activity patterns, which have been described in GnRH neurons from mammals. The type of activity pattern and spontaneous firing rate did ...
Zebrafish, 2006
Russell D. Fernald, Ph.D., is a Professor of Biological Sciences and the Benjamin Scott Crocker P... more Russell D. Fernald, Ph.D., is a Professor of Biological Sciences and the Benjamin Scott Crocker Professor in Human Biology at Stanford University (California). He received his Bachelor's degree from Swarthmore College (Swarthmore, PA) and his Ph.D. from the University of Pennsylvania (Philadelphia). Dr. Fernald completed a postdoctoral fellowship with Dr. O. Creutzfeldt at the Max-Planck-Institute for Psychiatry, in Munich, Germany, and a postdoctoral fellowship with Dr. Konrad Lorenz at the Max-Planck-Institute for Behavioral Physiology. In 2004 he shared the Rank Prize for discoveries about lens function. Dr. Fernald's lab uses an African cichlid fish species to study how social experience influences the brain and how retinal progenitor cell division and differentiation are controlled.
Vision Research, 1994
Refractive index distribution in the teleost crystalline lens was measured with a nondestructive ... more Refractive index distribution in the teleost crystalline lens was measured with a nondestructive method in freshly excised lenses of the African teleost fish Haplochromis burtoni. Independently, spherical aberration was measured in a parallel set of lenses. The measured refractive index profiles show a continual decrease of refractive index from the center to the surface of the lens. The H. burtoni lens is of high optical quality and slightly overcorrected for spherical aberration. Details of the small residual spherical aberration were accurately predicted by ray-tracing model calculations based on the measured refractive index profile. The refractive index profile and the spherical aberration both show more complex characteristics than suggested by earlier measurements and lens models.
Experientia, 1975
Zusammenfassung Wir haben die akustischen Signale bei sozialem Verhalten der afrikanischen Cichli... more Zusammenfassung Wir haben die akustischen Signale bei sozialem Verhalten der afrikanischen Cichliden-Fische,Haplochromis burtoni untersucht. Wir fanden keine Beweise dafür, dass diese Signale eine Kommunikationsfunktion haben.
Science, 2008
What genes and regulatory sequences contribute to the organization and functioning of neural circ... more What genes and regulatory sequences contribute to the organization and functioning of neural circuits and molecular pathways in the brain that support social behavior? How does social experience interact with information in the genome to modulate brain activity? Here, we address these questions by highlighting progress that has been made in identifying and understanding two key "vectors of influence" that link genes, the brain, and social behavior: (i) Social information alters gene expression in the brain to influence behavior, and (ii) genetic variation influences brain function and social behavior. We also discuss how evolutionary changes in genomic elements influence social behavior and outline prospects for a systems biology of social behavior. G enes and social behavior have long had a tempestuous relationship in both science and society, and the "nature-versus-nurture" debate still has its adherents. This controversy persists because the relations among genes, the brain, and social behavior have complex entanglements across several different time scales , ranging from organismal development and physiology all the way to evolutionary time . Genes do not specify behavior directly but rather encode molecular products that build and govern the functioning of the brain through which behavior is expressed. Brain development, brain activity, and behavior all depend on both inherited and environmental influences, and there is increasing appreciation that social information can alter brain gene expression and behavior. Furthermore, variation in behavior shapes the evolution of genomic elements that influence social behavior through the feedback of natural selection.
Regulatory Peptides, 1995
Proceedings of the Royal Society B: Biological Sciences, 2012
Proceedings of the Royal Society B: Biological Sciences, 2008
Neuropeptides have widespread modulatory effects on behaviour and physiology and are associated w... more Neuropeptides have widespread modulatory effects on behaviour and physiology and are associated with phenotypic transitions in a variety of animals. Arginine vasotocin (AVT) is implicated in mediating alternative male phenotypes in teleost fish, but the direction of the association differs among species, with either higher or lower AVT related to more territorial behaviour in different fishes. To clarify the complex relationship between AVT and alternative phenotype, we evaluated AVT expression in an African cichlid in which social status is associated with divergent behaviour and physiology. We compared AVT mRNA expression between territorial and non-territorial (NT) males in both whole brains and microdissected anterior preoptic areas using transcription profiling, and in individual preoptic nuclei using in situ hybridization. These complementary methods revealed that in the posterior preoptic area (gigantocellular nucleus), territorial males exhibit higher levels of AVT expression than NT males. Conversely, in the anterior preoptic area (parvocellular nucleus), AVT expression is lower in territorial males than NT males. We further correlated AVT expression with behavioural and physiological characteristics of social status to gain insight into the divergent functions of individual AVT nuclei. Overall, our findings highlight a complex association between AVT and social behaviour.
Proceedings of the National Academy of Sciences, 1994
In vertebrates, the gonadotropin-releasing hormone (GnRH) decapeptide is secreted from hypothalam... more In vertebrates, the gonadotropin-releasing hormone (GnRH) decapeptide is secreted from hypothalamic nerve terminals to regulate reproduction via control of synthesis and release of pituitary gonadotropins. Only one GnRH peptide has been found in mammals, with one exception, although numerous other vertebrate species express more than one of the eight known decapeptide forms as shown by immunocytochemical labeling of distinct cell groups in the brain. However, neither the functional nor the evolutionary relationships among these GnRH forms are clear, because only one preprohormone gene sequence from any species has been reported. The most ubiquitous alternative form of GnRH is
PLoS ONE, 2014
In social animals, hierarchical rank governs food availability, territorial rights and breeding a... more In social animals, hierarchical rank governs food availability, territorial rights and breeding access. Rank order can change rapidly and typically depends on dynamic aggressive interactions. Since the neuromodulator corticotrophin releasing factor (CRF) integrates internal and external cues to regulate the hypothalamic-pituitary adrenal (HPA) axis, we analyzed the CRF system during social encounters related to status. We used a particularly suitable animal model, African cichlid fish, Astatotilapia burtoni, whose social status regulates reproduction. When presented with an opportunity to rise in rank, subordinate A. burtoni males rapidly change coloration, behavior, and their physiology to support a new role as dominant, reproductively active fish. Although changes in gonadotropin-releasing hormone (GnRH1), the key reproductive molecular actor, have been analyzed during social ascent, little is known about the roles of CRF and the HPA axis during transitions. Experimentally enabling males to ascend in social rank, we measured changes in plasma cortisol and the CRF system in specific brain regions 15 minutes after onset of social ascent. Plasma cortisol levels in ascending fish were lower than subordinate conspecifics, but similar to levels in dominant animals. In the preoptic area (POA), where GnRH1 cells are located, and in the pituitary gland, CRF and CRF 1 receptor mRNA levels are rapidly down regulated in ascending males compared to subordinates. In the Vc/Vl, a forebrain region where CRF cell bodies are located, mRNA coding for both CRFR 1 and CRFR 2 receptors is lower in ascending fish compared to stable subordinate conspecifics. The rapid time course of these changes (within minutes) suggests that the CRF system is involved in the physiological changes associated with shifts in social status. Since CRF typically has inhibitory effects on the neuroendocrine reproductive axis in vertebrates, this attenuation of CRF activity may allow rapid activation of the reproductive axis and facilitate the transition to dominance.
Journal of Fish Biology, 2008
Gonadotropin-releasing hormone (GnRH) was originally identified because of its essential role in ... more Gonadotropin-releasing hormone (GnRH) was originally identified because of its essential role in regulating reproduction in all vertebrates. Since then, three phylogenetically related GnRH decapeptides have been characterized in vertebrates and invertebrates. Almost all tetrapods investigated have at least two GnRH forms (GnRH1 and GnRH2) in the central nervous system. From distributional and functional studies in vertebrates, GnRH1 in the hypothalamus projects predominantly to the pituitary and regulates reproduction via gonadotropin release. GnRH2, which is located in the midbrain, projects to the whole brain and is thought to be involved in sexual behaviour and food intake. GnRH3, located in the forebrain, has only been found in teleost fish and appears to be involved in sexual behaviour, as well as, in some fish species, gonadotropin release. Multiple GnRH receptors (GnRH-Rs), G-protein-coupled receptors regulate endocrine functions and neural transmissions in vertebrates. Phylogenetic and structural analyses of coding sequences show that all vertebrate GnRH-Rs cluster into two main receptor types comprised of four subfamilies. This suggests that at least two rounds of GnRH receptor gene duplications may have occurred in different groups within each lineage. Functional studies suggest that two particular subfamilies of GnRH receptors have independently evolved to act as species-specific endocrine modulators in the pituitary, and these show the greatest variety in regulating neuron networks in the brain. Given the long evolutionary history of the GnRH system, it seems likely that much more remains to be understood about its roles in behaviour and function of vertebrates.
Journal of Fish Biology, 1998
Electro-olfactogram (EOG) responses to a diverse range of steroid hormones were recorded in the A... more Electro-olfactogram (EOG) responses to a diverse range of steroid hormones were recorded in the African cichlid Haplochromis burtoni. Olfactory receptor responsiveness was sensitive to the attachment sites of sulphate and glucuronide groups. 1998 The Fisheries Society of the British Isles
Journal of Endocrinology, 2006
In many species, social interactions regulate reproductive capacity, although the exact mechanism... more In many species, social interactions regulate reproductive capacity, although the exact mechanisms of such regulation are unclear. Since social stress is often related to reproductive regulation, we measured the physiological signatures of change in reproductive state as they relate to short-term stress and the stress hormone cortisol. We used an African cichlid fish, Astatotilapia burtoni, with two distinct, reversible male phenotypes: dominant (territorial, T) males that are larger, more brightly colored, more aggressive, and reproductively competent and non-dominant males (non-territorial, NT) that are smaller, camouflage colored, and have regressed gonads. Male status, and hence reproductive competence, depends on social experience in this system. Specifically, if a T male is placed among larger male fish, it quickly becomes NT in behavior and coloration, but complete regression of its reproductive axis takes ca. 3 weeks . Reproduction in all vertebrates is controlled by the hypothalamic-pituitary-gonadal axis in which the key signaling molecule from the brain to the pituitary is GnRH1. Here, we subjected T males to territory loss, a social manipulation which results in status descent. We measured the effects of this status change in levels of circulating cortisol and testosterone as well as mRNA levels of GnRH1 and GnRH receptor-1 (GnRH-R1) in the brain and pituitary, respectively. Following short-term social suppression (4 h), no change was observed in plasma cortisol level, GnRH1 mRNA expression, GnRH-R1 mRNA expression, or plasma testosterone level. However, following a somewhat longer social suppression (24 h), cortisol and GnRH1 mRNA levels were significantly increased, and testosterone levels were significantly decreased. These results suggest that in the short run, deposed T males essentially mount a neural 'defense' against loss of status.
Journal of Comparative Physiology A: Sensory, Neural, and Behavioral Physiology, 1999
The focal length of the vertebrate eye is a function of wavelength, i.e. the eye suers from longi... more The focal length of the vertebrate eye is a function of wavelength, i.e. the eye suers from longitudinal chromatic aberration. Chromatic defocus is a particularly severe problem in eyes with high light-gathering ability, since depth of ®eld is small due to a pupillary opening that is large in relation to the focal length of the eye. Calculations show that in such eyes only a narrow spectral band of light can be in focus on the retina. For the major part of the visual spectrum, spatial resolution should be limited by the optics of the eye and far lower than the resolving power achievable by the retinal cone photoreceptor mosaic. To solve this problem, ®shes with irises unresponsive to light have developed lenses with multiple focal lengths. Well-focused images are created at the wavelengths of maximum absorbance of all spectral cone types. Multifocal lenses also appear to be present in some terrestrial species. In eyes with mobile irises, multifocal lenses are correlated with pupil shapes that allow all zones of the lens, with dierent refractive powers, to participate in the imaging process, irrespective of the state of pupil constriction.
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Papers by Russell Fernald