Biomedical subjects

R D Fernald

Publications and source records attributed to R D Fernald.

At least 19 recordsLinked to original sources

PubMed2001

The development of the crystalline lens is sensitive to visual input in the African cichlid fish, Haplochromis burtoni.

We investigated whether the development of the vertebrate crystalline lens is sensitive to visual input. The optical properties of fish lenses were examined as a function of lens size and the optical rearing conditions. Fish (Haplochromis burtoni, Cichlidae) were reared in white light (control group), under spectral deprivation (monochromatic lights), deprivation of the cone system (scotopic illumination), and complete visual deprivation (darkness). Longitudinal spherical aberrations (LSAs) and refractive index profiles of the lenses were measured with thin laser beams. The performance of the lens was modeled by ray-tracing calculations from measured LSAs. In lenses from the control group, LSA and f/R (focal length relative to lens radius) decreased as a function of age. The optical properties of the lenses were modified after rearing in darkness, scotopic illumination, and in monochromatic lights due to changes in the refractive index profile. Rearing in darkness and scotopic illumination reduced the optical quality of the lens. In animals reared under spectral deprivation, the lens did not create well-focused images for all spectral cone types in the same plane, as it does in animals reared in white light. We conclude that visual input seems to play an important role in the development of the lens. The control mechanisms remain unknown.

Animals↗

PubMed2001

Gonadotropin-releasing hormone receptor in the teleost Haplochromis burtoni: structure, location, and function.

GnRH acts via GnRH receptors (GnRH-R) in the pituitary to cause the release of gonadotropins that regulate vertebrate reproduction. In the teleost fish, Haplochromis burtoni, reproduction is socially regulated through the hypothalamus-pituitary-gonadal axis, making the pituitary GnRH-R a likely site of action for this control. As a first step toward understanding the role of GnRH-R in the social control of reproduction, we cloned and sequenced candidate GnRH-R complementary DNAs from H. burtoni tissue. We isolated a complementary DNA that predicts a peptide encoding a G protein-coupled receptor that shows highest overall identity to other fish type I GnRH-R (goldfish IA and IB and African catfish). Functional testing of the expressed protein in vitro confirmed high affinity binding of multiple forms of GNRH: Localization of GnRH-R messenger RNA using RT-PCR revealed that it is widely distributed in the brain and retina as well as elsewhere in the body. Taken together, these data suggest that this H. burtoni GnRH receptor probably interacts in vivo with all three forms of GNRH:

Amino Acid Sequence↗

PubMed2000

Social status controls somatostatin neuron size and growth.

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 ascending animals compared with those of dominant or socially descending fish. These results reveal possible mechanisms responsible for socially induced physiological plasticity that allow animals to shift resources from reproduction to growth or vice versa depending on the social context.

Animals↗

PubMed2000

Two molecular forms of gonadotropin-releasing hormone (GnRH-I and GnRH-II) are expressed by two separate populations of cells in the rhesus macaque hypothalamus.

Gonadotropin-releasing hormone represents the primary neuroendocrine link between the brain and the reproductive axis, and at least two distinct molecular forms of this decapeptide (GnRH-I and GnRH-II) are known to be expressed in the forebrain of rhesus macaques (Macaca mulatta). Although the distribution pattern of the two corresponding mRNAs is largely dissimilar, their expression appears to show some overlap in specific regions of the hypothalamus; this raises the possibility that some cells express both molecular forms of GnRH. To resolve this issue, double-label histochemistry was performed on hypothalamic sections from six male rhesus macaques, using a monoclonal antibody to GnRH-I and a riboprobe to monkey GnRH-II mRNA. In total, more than 2000 GnRH neurons were examined but in no instance were GnRH-I peptide and GnRH-II mRNA found to be coexpressed. This finding emphasizes that GnRH-I and GnRH-II are synthesized by two distinct populations of hypothalamic neurons, and suggests that they may be regulated by different neuroendocrine pathways.

Animals↗

PubMed2000

Evolution of eyes.

Seeing is important for most species and it has been a key selective advantage throughout evolution. Consequently, there is a remarkable diversity among types of eyes. Animals have converged on eight optical solutions for collecting and focusing light; in contrast, all eyes share the same molecular strategy for absorbing photons. Recent studies have identified similarities in the genetic information that is used in the development of eyes, leading to the hypothesis that distinctly different eye types might have had a monophyletic origin. Across many species, there is a remarkable continuity of the developmental genes that participate in the construction of similar--but not necessarily homologous--eyes.

Animals↗

PubMed1999

Social status regulates growth rate: consequences for life-history strategies.

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 (Günther) 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.

Animals↗

PubMed1999

Nasotemporal asymmetry during teleost retinal growth: preserving an area of specialization.

Teleost fish retinas grow throughout adult life through both cell addition and stretching. Cell division occurs at the periphery of the retina, resulting in annular addition of all cell types except rod photoreceptors, which are added in the central retina. Since many teleosts have a region of high cellular density at the temporal pole of the eye, we analyzed whether and how this specialized region of high visual acuity maintained its relative topographical position through asymmetric circumferential growth. To do this, we measured the pattern of long-term retinal growth in the African cichlid Haplochromis burtoni. We found that the retina expands asymmetrically along the nasotemporal axis, with the nasal retina growing at a higher rate than the temporal, dorsal, or ventral retinae, whose growth rates are equal. This nasotemporal asymmetry is produced via significantly greater expansion of retinal tissue at the nasal pole rather than through differential cell proliferation. The mechanisms responsible for this differential retinal enlargement are unknown; however, such asymmetric expansion very likely minimizes disruption in vision during rapid growth.

Animals↗

PubMed1999

Second form of gonadotropin-releasing hormone in mouse: immunocytochemistry reveals hippocampal and periventricular distribution.

Hypothalamic GnRH (GnRH-I) is known and named for its role in regulating reproductive function in vertebrates by controlling release of gonadotropins from the pituitary. However, another form of GnRH of unknown function (pGlu-His-Trp-Ser-His-Gly-Trp-Tyr-Pro-Gly; GnRH-II) is expressed in the mesencephalon of all vertebrate classes except jawless fish. Here we show with immunocytochemical staining that the GnRH-II peptide is localized to the mouse midbrain as in other vertebrates, as well as in cells surrounding the ventricles and in cells adjacent to the hippocampus. Staining of adjacent sections using GnRH-I antibody revealed that the distribution of GnRH-I does not overlap with that of GnRH-II.

Animals↗

PubMed1999

Gonadotropin-releasing hormone genes: phylogeny, structure, and functions.

Gonadotropin-releasing hormone (GnRH, previously called leutinizing hormone-releasing hormone, LHRH) is the final common signaling molecule used by the brain to regulate reproduction in all vertebrates. Recently, genes encoding two other GnRH forms have been discovered. Here we present a phylogenetic analysis that shows that the GnRH genes fall naturally into three distinct branches, each of which shares not only a molecular signature but also characteristic expression sites in the brain. The GnRH genes appear to have arisen through gene duplication from a single ancestral GnRH whose origin predates vertebrates. Several lines of data support this suggestion, including the fact that all three genes share an identical exonic structure. The existence of three distinct GnRH families suggests a new, natural nomenclature for the genes, and in addition, we present a logical proposal for naming the peptide sequences. The two recently discovered GnRH genes are unusual because they encode decapeptides that are identical in all the species in which they have been found. The control of gene expression also differs among the three gene families as might be expected since they have had separate evolutionary trajectories for perhaps 500 million years.

Animals↗

PubMed1999

Multifocal lenses compensate for chromatic defocus in vertebrate eyes.

The focal length of the vertebrate eye is a function of wavelength, i.e. the eye suffers from longitudinal chromatic aberration. Chromatic defocus is a particularly severe problem in eyes with high light-gathering ability, since depth of field 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, fishes 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 different refractive powers, to participate in the imaging process, irrespective of the state of pupil constriction.

Animals↗

PubMed1999

Regional expression of mRNA encoding a second form of gonadotropin-releasing hormone in the macaque brain.

In mammals, reproduction is thought to be controlled by a single neuropeptide, gonadotropin-releasing hormone (GnRH-I), which regulates the synthesis and secretion of gonadotropins from the pituitary gland. However, another form of this decapeptide (GnRH-II), of unknown function, also exists in the brain of many vertebrate species, including humans; it is encoded by a different gene and its amino acid sequence is 70% identical to that of GnRH-I. Here we report the cloning of a GnRH-II cDNA from the rhesus macaque (Macaca mulatta), and show for the first time by in situ hybridization that GnRH-II mRNA is expressed in the primate midbrain, hippocampus and discrete nuclei of the hypothalamus, including the supraoptic, paraventricular, suprachiasmatic and arcuate. Because the regional distribution pattern of cells containing GnRH-II mRNA is largely dissimilar to that of cells containing GnRH-I mRNA, it is likely that these two cell populations receive distinct neuroendocrine inputs and thus regulate GnRH synthesis and release differently.

Amino Acid Sequence↗

PubMed1998

Cell death precedes rod neurogenesis in embryonic teleost retinal development.

We measured cell death in the retinas of embryonic and adult teleost fish using TUNEL staining. Following a wave of cell birth during embryogenesis that generates all retinal cell types except rods, cell death occurs in all three nuclear layers. The lack of a corresponding pattern of cell death in the growing adult margin suggests different roles for death during embryogenesis and adult neurogenesis.

Animals↗

PubMed1998

The embryogenesis of rod photoreceptors in the teleost fish retina, Haplochromis burtoni.

Development of the retina, like that of other tissues, occurs via an orderly sequence of cell division and differentiation, producing the functional retina. In teleost fish, however, cell division and differentiation in the retina continue throughout the life of the animal in two distinct ways. Stem cells in a circumferential germinal zone at the periphery of the retina give rise to all retinal cell types and progenitor cells located throughout the retina in the outer nuclear layer (ONL) produce new rod photoreceptors. These processes in adult retina recapitulate in space the embryonic events responsible for forming the retina. Analysis of these events in an African cichlid fish, Haplochromis burtoni, confirmed that cone photoreceptors differentiate first, followed by rod photoreceptors. Correspondingly, at the margin of the eye, cone photoreceptors differentiate nearer to the margin than do rods. Control of photoreceptor production is not understood. Here we present the time of appearance and distribution pattern of GABA and vimentin which are candidates for the control of retinal cell division and differentiation. Antibody staining reveals that both GABA and vimentin exhibit unique patterns of expression during embryonic retinal development. Vimentin immunoreactivity is evident throughout the retina in a spoke-like pattern between developmental Days 4 and 7, as both cone and rod photoreceptors are being formed. GABA is expressed in horizontal cells between Days 5 and 7, corresponding to the onset of rod differentiation in time and in position within the retina. Moreover, the wave of GABAergic staining in the horizontal cells parallels the wave of rod differentiation across the embryonic retina of H. burtoni. Thus, GABA may play a role in the development of rod photoreceptors.

Animals↗

PubMed1998

Second gene for gonadotropin-releasing hormone in humans.

Gonadotropin-releasing hormone (GnRH) is a decapeptide widely known for its role in regulating reproduction by serving as a signal from the hypothalamus to pituitary gonadotropes. In addition to hypothalamic GnRH (GnRH-I), a second GnRH form (pGln-His-Trp-Ser-His-Gly-Trp-Tyr-Pro-Gly; GnRH-II) with unknown function has been localized to the midbrain of many vertebrates. We show here that a gene encoding GnRH-II is expressed in humans and is located on chromosome 20p13, distinct from the GnRH-I gene that is on 8p21-p11.2. The GnRH-II genomic and mRNA structures parallel those of GnRH-I. However, in contrast to GnRH-I, GnRH-II is expressed at significantly higher levels outside the brain (up to 30x), particularly in the kidney, bone marrow, and prostate. The widespread expression of GnRH-II suggests it may have multiple functions. Molecular phylogenetic analysis shows that this second gene is likely the result of a duplication before the appearance of vertebrates, and predicts the existence of a third GnRH form in humans and other vertebrates.

Adult↗

PubMed1998

Genomic structure and expression sites of three gonadotropin-releasing hormone genes in one species.

In the teleost fish, Haplochromis burtoni, gonadotropin-releasing hormone (GnRH) peptide has been localized to three distinct regions in the brain. Each GnRH population is associated with expression of a distinct cDNA as previously described. Here we report the complete genomic sequences encoding these three forms and compare their structural organization, putative regulatory elements, and expression patterns in the body. All three genes share a common structure of four exons: the first exon encodes the 5' untranslated region; the second exon encodes the signal sequence, GnRH decapeptide, and the 5' end of the GnRH-associated peptide (GAP); the third exon consists entirely of GAP coding sequence; and the fourth exon encodes the 3' end of GAP and the 3' untranslated region. Each of the three GnRH genes has been shown previously to have a distinct spatial expression pattern in the brain, and here we use reverse transcription and cDNA amplification to demonstrate that each gene is expressed in the body. The gene encoding the releasing form, ¿Ser8¿GnRH, is expressed in the heart, liver, spleen, kidney, and testis, as well as in the preoptic area. The ¿His5Trp7Tyr8¿GnRH gene is expressed in the testis as well as in the midbrain. The ¿Trp7Leu8¿GnRH gene is expressed in the testis and the terminal nerve area. We examined the 500 bp upstream of exon 1 in all three H. burtoni genes and identified putative binding sites for glucocorticoid receptor, androgen receptor, and progesterone receptor, as well as the transcription factors Ap-1 and Sp-1. The genomic sequence encoding the terminal nerve form of GnRH (i.e., ¿Trp7Leu8¿GnRH) in H. burtoni is remarkably similar to that encoding the presumed releasing form of GnRH in salmonids, especially in the 3' intergenic region. Taken together with phylogenetic and mRNA localization data in salmonids, these data suggest that the gene encoding the releasing form of GnRH in salmonids may not yet be described.

Animals↗

PubMed1998

Ontogeny of gonadotropin-releasing hormone (GnRH) gene expression reveals a distinct origin for GnRH-containing neurons in the midbrain.

In the teleost fish, Haplochromis burtoni, three gonadotropin-releasing hormone (GnRH) peptides and their corresponding cDNA sequences and full-length genes have previously been reported. Here we describe the ontogeny of mRNA expression for these three GnRH forms in H. burtoni. Each of the three forms has been shown to have a distinct spatial expression pattern in the adult brain. ¿Ser8¿GnRH (the releasing form) is expressed exclusively in the hypothalamus, ¿His5Trp7Tyr8¿GnRH is expressed in the midbrain mesencephalon, and ¿Trp7Leu8¿GnRH is expressed in the terminal nerve area of the telencephalon. Previous work in other animals has shown that GnRH-containing neurons in the preoptic area arise from the olfactory placode and that these cells migrate into their final positions in the brain during early development. By using molecular probes to identify the cell types expressing distinct GnRH forms, our data are consistent with the migration of both ¿Ser8¿GnRH and ¿Trp7Leu8¿GnRH neurons from the placode to their appropriate adult locations in the brain. In contrast, we show that ¿His5Trp7Tyr8¿GnRH neurons arise from the germinal zone of the third ventricle. By using in situ hybridization with digoxigenin-labeled cRNA probes, ¿His5Trp7Tyr8¿GnRH mRNA was first evident at day 4, ¿Trp7Leu8¿GnRH mRNA at day 8, and ¿Ser8¿GnRH mRNA at day 14. However, by using the reverse-transcriptase polymerase chain reaction (RT-PCR), all three GnRH mRNAs were found in whole embryos at day 4 of the 14 days of embryogenesis. This striking difference may be due to the greater sensitivity of RT-PCR compared with in situ hybridization. Alternatively, it is possible that ¿Ser8¿GnRH and ¿Trp7Leu8¿GnRH are expressed outside the brain during early development and only later inside the brain.

Animals↗

PubMed1997

Cell movement and cell cycle dynamics in the retina of the adult teleost Haplochromis burtoni.

The authors analyzed the pattern of neurogenesis, the time frame of cell movement, and the cell cycle kinetics of a population of stem cells located in the outer nuclear layer in the retina of the adult teleost Haplochromis burtoni. These stem cells continue to give rise to new rod photoreceptors throughout life. The new rods move vitread after the last cell division. The authors investigated events during cell division and cell differentiation by using one marker that labels dividing cells transiently (proliferating cell nuclear antigen) along with another marker that labels dividing cells permanently (bromodeoxyuridine). The bulk of cell movement does not occur within 24 hours after S-phase labeling but is clearly underway 12 hours later, shortly after mitosis. The cell cycle length was estimated to be approximately 25 hours. The distribution of labeled cells at various times after S-phase suggests that new rods are generated by asymmetric cell division, that is, one of the daughter cells moves after mitosis and becomes postmitotic, while the other daughter cell remains in place and reenters the cell cycle. The proliferation patterns across the retina suggest that the location of areas of mitotic activity changes over time. The authors hypothesize that local extracellular factors control the rate of cell division in a given area, thereby keeping the overall rod density constant.

Animals↗

PubMed1997

Stress and dominance in a social fish.

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. Social behavior may lead to changes in reproductive state through integration of cortisol changes in time. Thus, information available from the stress pathway may provide socially relevant signals to produce neural change.

Animals↗