Cardiac regeneration in non-mammalian vertebrates

The heart is a robust organ, capable of pumping nutrients and transferring oxygen throughout the body via a network of capillaries, veins and arteries, for the entirety of a human's life. However, the fragility of mammalian hearts is also evident when it becomes damaged and parts of the organ fail to function. This is due to the fact that rather than replenishing the damaged areas with functional cellular mass, fibrotic scar tissue is the preferred replacement, resulting in an organ with functional deficiencies. Due to the mammalian hearts incapability to regenerate following damage and the ever-increasing number of people worldwide suffering from heart disease, tireless efforts are being made to discover ways of inducing a regenerative response in this most important organ. One such avenue of investigation involves studying our distantly related non-mammalian vertebrate cousins, which over the last decade has proved to us that cardiac regeneration is possible. This review will highlight these organisms and provide insights into some of the seminal discoveries made in the heart regeneration field using these amazing chordates.     

Ghrelin: a multifunctional hormone in non-mammalian vertebrates

In mammals, ghrelin is a non-amidated peptide hormone, existing in both acylated and non-acylated forms, produced mainly from the X/A or ghrelin cells present in the mucosal layer of the stomach. Ghrelin is a natural ligand of the growth hormone (GH) secretagogue-receptor (GHS-R), and functions primarily as a GH-releasing hormone and an orexigen, as well as having several other biological actions. Among non-mammalian vertebrates, amino acid sequence of ghrelin has been reported in two species of cartilaginous fish, seven species of teleosts, two species of amphibians, one species of reptile and six species of birds. The structure and functions of ghrelin are highly conserved among vertebrates. This review presents a concise overview of ghrelin biology in non-mammalian vertebrates.     

Homologue of mammalian apolipoprotein A-II in non-mammalian vertebrates

Although apolipoprotein with molecular weight 14 kDa （apo-14kDa） is associated with fish plasma highdensity lipoproteins （HDLs）, it remains to be determined whether apo-14 kDa is the homologue of mammalian apoA-II. We have obtained the full eDNA sequences that encode Japanese eel and rainbow trout apo-14 kDa. Homologues of Japanese eel apo-14 kDa sequence could be found in 14 fish species deposited in the DDBJ/EMBL/GenBank or TGI database. Fish apo- 14 kDa lacks propeptide and contains more internal repeats than mammalian apoA-II. Nevertheless, phylogenetic analysis allowed fish apo-14 kDa to be the homologue of mammalian apoA-II. In addition, in silico cloning of the TGI, Ensembl, or NCBI database revealed apoA-IIs in dog, chicken, green anole lizard, and African clawed frog whose sequences had not so far been available, suggesting both apoA-I and apoA-II as fundamental constituents of vertebrate HDLs.     

Erythrocyte sorbitol dehydrogenase of selected non-mammalian vertebrates

Erythrocyte sorbitol dehydrogenase activity (EC 1.1.1.14) from selected non-mammalian vertebrates was studied showing great variability not related to their phylogenetical position. The Michaelis-Menten constant (Km) for sorbitol exhibited moderate low values in the studied animals. In snakes the Km for sorbitol was low with moderate activity of sorbitol dehydrogenase, suggesting that the enzyme could reach maximum activity with lower sorbitol concentration in comparison to other vertebrates. In the snakes the enzyme showed the same affinity for all the studied polyols, indicating that we are probably dealing with a very ancient enzyme, an unspecific enzyme.     

Ghrelin: a multifunctional hormone in non-mammalian vertebrates.

In mammals, ghrelin is a non-amidated peptide hormone, existing in both acylated and non-acylated forms, produced mainly from the X/A or ghrelin cells present in the mucosal layer of the stomach. Ghrelin is a natural ligand of the growth hormone (GH) secretagogue-receptor (GHS-R), and functions primarily as a GH-releasing hormone and an orexigen, as well as having several other biological actions. Among non-mammalian vertebrates, amino acid sequence of ghrelin has been reported in two species of cartilaginous fish, seven species of teleosts, two species of amphibians, one species of reptile and six species of birds. The structure and functions of ghrelin are highly conserved among vertebrates. This review presents a concise overview of ghrelin biology in non-mammalian vertebrates.     

Sex chromosome evolution and speciation in Ficedula flycatchers

Speciation is the combination of evolutionary processes that leads to the reproductive isolation of different populations. We investigate the significance of sex-chromosome evolution on the development of post- and prezygotic isolation in two naturally hybridizing Ficedula flycatcher species. Applying a tag-array-based mini-sequencing assay to genotype single nucleotide polymorphisms (SNPs) and interspecific substitutions, we demonstrate rather extensive hybridization and backcrossing in sympatry. However, gene flow across the partial postzygotic barrier (introgression) is almost exclusively restricted to autosomal loci, suggesting strong selection against introgression of sex-linked genes. In addition to this partial postzygotic barrier, character displacement of male plumage characteristics has previously been shown to reinforce prezygotic isolation in these birds. We show that male plumage traits involved in reinforcing prezygotic isolation are sex linked. These results suggest a major role of sex-chromosome evolution in mediating post- and prezygotic barriers to gene flow and point to a causal link in the development of the two forms of reproductive isolation.     

Regulatory peptides and control of food intake in non-mammalian vertebrates

The current view of the control of food intake involves a central feeding system in the hypothalamus receiving input from peripheral systems. The presence of food in the gut stimulates the release of several regulatory peptides that control gut motility and secretion. Some of these peptides also act as feedback satiety signals, responsible for termination of a meal. Among the regulatory peptides suggested as peripheral satiety signals are cholecystokinin and gastrin releasing peptide. A more long-term peripheral regulation of food intake has also been postulated and leptin has been suggested as a regulator of food intake. Several regulatory peptides mediate orexigenic or anorexigenic effects in the central feeding system. Neuropeptide Y and galanin both act centrally and stimulate the intake of food, while corticotropin releasing factor reduces food intake. At present, most information about the regulation of food intake is gained from mammalian studies and these findings are used as a base for a discussion on the current knowledge of how regulatory peptides control appetite in non-mammalian vertebrates.     

Distribution of rod- and cone-specific phosducins in retinas of non-mammalian vertebrates

In mammalian retinas, it has been believed that just one kind of phosducin (PD) commonly exists in both rods and cones. However, we have previously reported that there are rod- and cone-specific PDs (OlPD-R and OlPD-C) in medaka (Oryzias latipes) retina [FEBS Lett., 502, 117-121, 2001]. To clarify the distribution and evolution of these photoreceptor type-specific PDs, we investigated PDs of another teleost and a reptile. Immunohistochemical and Western blot analyses using anti-medaka PD antisera demonstrated that two kinds of PDs are expressed in zebrafish (Danio rerio) photoreceptor cells. Our study is suggestive that teleosts generally possess rod- and cone-specific PDs. We isolated a cDNA encoding putative PD (PmlPD) of a diurnal gecko (Phelsuma madagascariensis longinsulae). Because diurnal gecko possesses a pure-cone retina, it was expected that PmlPD would be expressed in cones. Molecular phylogenetic analysis demonstrated that PmlPD was more closely related to mammalian PDs than teleost cone-specific PDs, suggesting that the rod- and cone-specific subtype of teleost PDs have arisen after the teleost-tetrapod divergence.     

Sex chromosome evolution in the clam shrimp,Eulimnadia texana

Chromosomes that determine sex are predicted to evolve differently than autosomes: a lack of recombination on one of the two sex chromosomes is predicted to allow an accumulation of deleterious alleles that eventually leads to reduced functionality and potential physical degradation of the nonrecombining chromosome. Because these changes should occur at an elevated evolutionary rate, it is difficult to find appropriate species in which to test these evolutionary predictions. The unique genetic sex‐determining mechanism of the crustacean Eulimnadia texana prevents major chromosome degeneration because of expression of both ‘proto‐sex’ (i.e. early stage of development) chromosomes in homozygous form (ZZ and WW). Herein, we exploit this unique genetic system to examine the predicted accumulation of deleterious alleles by comparing both homogametic sexual types to their heterogametic counterpart. We report differences in crossing over in a sex‐linked region in the ZW hermaphrodites (～ 3%) relative to the ZZ males (～ 21%), indicative of cross‐over suppression in the ZW hermaphrodites. Additionally, we report that both ZZ and WW genotypes have reduced fitness relative to ZW hermaphrodites, which is consistent with the prediction of harboured recessive mutations embedded on both the Z and the W chromosomes. These results suggest that the proto‐sex chromosomes in E. texana accumulate recessive deleterious alleles. We hypothesize that recessive deleterious alleles of large effect cannot accumulate because of expression in both ZZ and WW individuals, keeping both chromosomes from losing significant function.     

Comparative aspects of natriuretic peptide physiology in non-mammalian vertebrates: a review

The natriuretic peptide system is a complex family of peptides and receptors that is primarily linked to the maintenance of osmotic and cardiovascular homeostasis. A natriuretic peptide system is present in each vertebrate class but there are varying degrees of complexity in the system. In agnathans and chondrichthyians, only one natriuretic peptide has been identified, while new data has revealed that multiple types of natriuretic peptides are present in bony fish. However, it seems in tetrapods that there has been a reduction in the number of natriuretic peptide genes, such that only three natriuretic peptides are present in mammals. The peptides act via a family of guanylyl cyclase receptors to generate the second messenger cGMP, which mediates a range of physiological effects at key targets such as the gills, kidney and the cardiovascular system. This review summarises the current knowledge of the natriuretic peptide system in non-mammalian vertebrates and discusses the physiological actions of the peptides.Abbreviations ANP atrial natriuretic peptide - AVT arginine vasotocin - BNP brain natriuretic peptide - cDNA complementary deoxyribonucleic acid - CNP C-type natriuretic peptide - cAMP adenosine 3, 5 cyclic monophosphate - cGMP guanosine 3, 5 cyclic monophosphate - GC guanylyl cyclase - GFR glomerular filtration rate - mRNA messenger ribonucleic acid - NPR natriuretic peptide receptor - NPs natriuretic peptides - sCP salmon cardiac peptide - VIP vasoactive intestinal peptide - VNP ventricular natriuretic peptide Communicated by I.D. Hume     

Mitotic chromosome condensation in vertebrates

Work from several laboratories over the past 10-15 years has revealed that, within the interphase nucleus, chromosomes are organized into spatially distinct territories [T. Cremer, C. Cremer, Chromosome territories, nuclear architecture and gene regulation in mammalian cells, Nat. Rev. Genet. 2 (2001) 292-301 and T. Cremer, M. Cremer, S. Dietzel, S. Muller, I. Solovei, S. Fakan, Chromosome territories-a functional nuclear landscape, Curr. Opin. Cell Biol. 18 (2006) 307-316]. The overall compaction level and intranuclear location varies as a function of gene density for both entire chromosomes [J.A. Croft, J.M. Bridger, S. Boyle, P. Perry, P. Teague,W.A. Bickmore, Differences in the localization and morphology of chromosomes in the human nucleus, J. Cell Biol. 145 (1999) 1119-1131] and specific chromosomal regions [N.L. Mahy, P.E. Perry, S. Gilchrist, R.A. Baldock, W.A. Bickmore, Spatial organization of active and inactive genes and noncoding DNA within chromosome territories, J. Cell Biol. 157 (2002) 579-589] (Fig. 1A, A'). In prophase, when cyclin B activity reaches a high threshold, chromosome condensation occurs followed by Nuclear Envelope Breakdown (NEB) [1]. At this point vertebrate chromosomes appear as compact structures harboring an attachment point for the spindle microtubules physically recognizable as a primary constriction where the two sister chromatids are held together. The transition from an unshaped interphase chromosome to the highly structured mitotic chromosome (compare Figs. 1A and B) has fascinated researchers for several decades now; however a definite picture of how this process is achieved and regulated is not yet in our hands and it will require more investigation to comprehend the complete process. From a biochemical point of view a vertebrate mitotic chromosomes is composed of DNA, histone proteins (60%) and non-histone proteins (40%) [6]. I will discuss below what is known to date on the contribution of these two different classes of proteins and their co-operation in establishing the final mitotic chromosome structure.     

Immunocytochemical identification of neurophysin-secreting neurons in the hypothalamo-neurohypophysial system of some non-mammalian vertebrates

Antiserum raised against a mammalian neurophysin, porcine neurophysin-II, was used in conjugation with the immunoperoxidase histochemical technique to detect neurophysin in the hypothalamus of the chickens, frog and goldfish. In the chickens, the paraventricular and supraoptic nuceli as well as the internal and external zones of the median eminence stained for neurophysin. Material in the perikarya of the frog and goldfish preoptic nucleus also cross-reacted immunologically against anti-porcine neurophysin-II serum. Serial dilutions of the anti-mammalian neurophysins serum were carried out in order to ascertain at which point the 3-layer immunocytochemical reaction ceased to localize neurophysin. In the chicken, frog and goldfish as well as in the rat, neurosecretory structures became difficult to visualize between 12800 and 25400 fold dilution of antiserum. The results demonstrate that the immunological cross-reactivity previously observed between an anti-mammalian neurophysin serum and the neurophysin isolated from mammals of varying phylogeny also extends to certain non-mammalian vertebrates and is suggestive of a structural homology of neurophysin from different species.     

Sex chromosome evolution: life,death and repetitive DNA

Dimorphic sex chromosomes create problems. Males of many species, including Drosophila, are heterogametic, with dissimilar X and Y chromosomes. The essential process of dosage compensation modulates the expression of X-linked genes in one sex to maintain a constant ratio of X to autosomal expression. This involves the regulation of hundreds of dissimilar genes whose only shared property is chromosomal address. Drosophila males dosage compensate by up regulating X-linked genes 2 fold. This is achieved by the Male Specific Lethal (MSL) complex, which is recruited to genes on the X chromosome and modifies chromatin to increase expression. How the MSL complex is restricted to X-linked genes remains unknown. Recent studies of sex chromosome evolution have identified a central role for 2 types of repetitive elements in X recognition. Helitrons carrying sites that recruit the MSL complex have expanded across the X chromosome in at least one Drosophila species.¹ Our laboratory found that siRNA from an X-linked satellite repeat promotes X recognition by a yet unknown mechanism.² The recurring adoption of repetitive elements as X-identify elements suggests that the large and mysterious fraction of the genome called “junk” DNA is actually instrumental in the evolution of sex chromosomes.     

Sex chromosome evolution in fish: the formation of the neo-Y chromosome in Eigenmannia (Gymnotiformes)

Chromosomes of a species of Eigenmannia presenting a X₁X₁X₂X₂:X₁X₂Y sex chromosome system, resulting from a Y-autosome Robertsonian translocation, were analyzed using the C-banding technique, chromomycin A₃ (CMA₃) and mithramycin (MM) staining and in situ digestion by the restriction endonuclease AluI. A comparison of the metacentric Y chromosome of males with the corresponding acrocentrics in females indicated that a C-band-positive, CMA₃/MM-fluorescent and AluI digestion-resistant region had been lost during the process of translocation, resulting in a diminution of heterochromatin in the males. It is hypothesized that the presence of a smaller amount of G+C-rich heterochromatin in the sex chromosomes of the heteromorphic sex when compared with the homomorphic sex may be associated with the sex determination mechanism in this species and may be a more widely occurring phenomenon in fish with differentiated sex chromosomes than was initially thought. Received: 1 April 1999; in revised form: 16 October 1999 / Accepted: 4 December 1999