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Biomedical subjects

Russell D Fernald

Publications and source records attributed to Russell D Fernald.

24 records · Page 2Linked to original sources

Eyes: variety, development and evolution.

The selective advantages of using light as a source of information are reflected in the diverse types of extant eyes. The physical properties of light restrict how it can be collected and processed, resulting in only eight known optical systems found in animals. Eyes develop through tissue rearrangement and differentiation. Our understanding of the source of genetic information used in developmental programs is growing rapidly and reveals distributions of gene expression with substantial overlap in both time and space. Specific genes and their products are used repeatedly, making causal relationships more difficult to discern. The phenomenon of groups of genes acting together seems to be the rule. Throughout evolution, particular genes have become associated with distinct aspects of eye development, and these suites of genes have been recruited repeatedly as new eyes evolved.

Animals↗

Evolving eyes.

Despite the incredible diversity among extant eyes, laws of physics constrain how light can be collected resulting in only eight known optical systems in animal eyes. Surprisingly, all animal eyes share a common molecular strategy using opsin for catching photons, but there are a diverse collection of mechanisms with proteins unrelated to each other used to focus light for vision. However, opsin is expressed in either one of two types of photoreceptor that differ fundamentally in their structure and tissue of origin. Taken together, this collection of observations strongly suggests that eyes have had multiple origins with remarkable convergence due to physics and molecular conservation of the opsin protein. Yet recent work has shown that a family of conserved genes are involved in eye formation despite substantial differences in their structure and origin, leading to a controversy over whether eyes evolved once or repeatedly. A likely resolution of this discussion is that particular genes and genetic programs have become associated with specific features needed for eyes and such suites of genes have been recruited as new eyes evolve. Since specific genes and their products are used repeatedly, it is somewhat difficult to conceptualize their causal relationships relative to evolutionary processes. However, detailed comparison of developmental programs may offer clues about multiple origins.

Animals↗

Multiple corticosteroid receptors in a teleost fish: distinct sequences, expression patterns, and transcriptional activities.

Corticosteroid hormones, including the mineralocorticoids and the glucocorticoids, regulate diverse physiological functions in vertebrates. These hormones act through two classes of corticosteroid receptors (CR) that are ligand-dependent transcription factors: type I or mineralocorticoid receptor (MR) and type II or glucocorticoid receptor (GR). There is substantial overlap in the binding of these two receptor types to hormones and to DNA. In fish, the overlap in processes controlled by CRs may be different from that in other vertebrates, as fish are thought to synthesize only glucocorticoids, whereas they express both GR and MR. Here we describe the characterization of four CRs in a cichlid fish, Haplochromis burtoni: a previously undescribed GR (HbGR1), another GR expressed in two splice isoforms (HbGR2a and HbGR2b), and an MR (HbMR). Sequence comparison and phylogenetic analysis showed that these CRs sort naturally into GR and MR groups, and that the GR duplication we describe will probably be common to all teleosts. Quantitative PCR revealed differential patterns of CR tissue expression in organs dependent on corticosteroid action. Trans-activation assays demonstrated that the CRs were selective for corticosteroid hormones and showed that the HbMR was similar to mammalian MRs in being more sensitive to both cortisol and aldosterone than the GRs. Additionally, the two HbGR2 isoforms were expressed uniquely in different tissues and were functionally distinct in their actions on classical GR-sensitive promoters. The identification of four CR subtypes in teleosts suggests a more complicated corticosteroid signaling in fish than previously recognized.

Amino Acid Sequence↗

Social regulation of gonadotropin-releasing hormone.

Behavioral interactions among social animals can regulate both reproductive behavior and fertility. A prime example of socially regulated reproduction occurs in the cichlid fish Haplochromis burtoni, in which interactions between males dynamically regulate gonadal function throughout life. This plasticity is mediated by the brain, where neurons that contain the key reproductive regulatory peptide gonadotropin-releasing hormone (GnRH) change size reversibly depending on male social status. To understand how behavior controls the brain, we manipulated the social system of these fish, quantified their behavior and then assessed neural and physiological changes in the reproductive and stress axes. GnRH gene expression was assessed using molecular probes specific for the three GnRH forms in the brain of H. burtoni. We found that perception of social opportunity to increase status by a male leads to heightened aggressiveness, to increased expression of only one of the three GnRH forms and to increases in size of GnRH-containing neurons and of the gonads. The biological changes characteristic of social ascent happen faster than changes following social descent. Interestingly, behavioral changes show the reverse pattern: aggressive behaviors emerge more slowly in ascending animals than they disappear in descending animals. Although the gonads and GnRH neurons undergo similar changes in female H. burtoni, regulation occurs via endogenous rather than exogenous social signals. Our data show that recognition of social signals by males alters stress levels, which may contribute to the alteration in GnRH gene expression in particular neurons essential for the animal to perform in its new social status.

Aggression↗

Social regulation of the brain: sex, size and status.

Fish comprise the largest group of extant vertebrates with approximately 25,000 known species. Some of these species are exceptional among vertebrates because they can change sex as adults. This observation raises ultimate questions about what selective forces led to the evolution of sex-changing ability and raises proximate questions about what mechanisms could account for this process. Sex change can be either from female to male (protogyny) or the reverse (protandry). In either case, the actual process of sex reversal requires reorganization of many critically important physiological systems from transformation of the gonads to modification of the neural and hormonal control systems. All of these changes require an individual animal to initiate the process based on information gleaned from the social situation. This is all the more remarkable because the information could be as simple as size discrimination or as complex as detecting subtle behavioural signals. Although it is self-evident that the brain controls behaviour, clearly behaviour can also 'control' the brain. How does behaviour cause changes in the brain? The work described here links molecular events with organismal behaviour by using an African cichlid fish model system in which social behaviours regulate reproduction. These animals have a complex social system based on the behaviour of two distinct classes of males, those with territories and those without. Changes in social status produced by behavioural interactions cause changes in neurons and endocrine responses. Surprisingly, growth rate is also regulated by social status and prior social history. Discovering how relevant social information is transduced into physiological processes requiring cellular and molecular action presents a major challenge.

Animals↗

Diurnal rhythm of cone opsin expression in the teleost fish Haplochromis burtoni.

The biochemical and morphological specializations of rod and cone photoreceptors reflect their roles in sight. The apoprotein opsin, which converts photons into chemical signals, functions at one end of these highly polarized cells, in the outer segment. Previous work has shown that the mRNA of rod opsin, the opsin specific to rods, is renewed in the outer segment with a diurnal rhythm in the retina of the teleost fish Haplochromis burtoni. Here we show that in the same species, all three cone opsin mRNAs (blue, green, and red) also have a diurnal rhythm of expression. Quantitative real-time polymerase chain reaction (PCR) with primer pairs specific for the cone photoreceptor opsin subtypes was used to detect opsin mRNA abundance in animals sacrificed at 3-h intervals around the clock. All three cone opsins were expressed with diurnal rhythms similar to each other but out of phase with the rod opsin rhythm. Specifically, cone opsin expression occurs at a higher level near the onset of the dark period, when cones are not used for vision. Finally, we found that the rhythm of cone opsin expression in fish appears to be light dependent, as prolonged darkness changes normal diurnal expression patterns.

Animals↗