Conservation and co-option in developmental programmes: the importance of homology relationships

One of the surprising insights gained from research in evolutionary developmental biology (evo-devo) is that increasing diversity in body plans and morphology in organisms across animal phyla are not reflected in similarly dramatic changes at the level of gene composition of their genomes. For instance, simplicity at the tissue level of organization often contrasts with a high degree of genetic complexity. Also intriguing is the observation that the coding regions of several genes of invertebrates show high sequence similarity to those in humans. This lack of change (conservation) indicates that evolutionary novelties may arise more frequently through combinatorial processes, such as changes in gene regulation and the recruitment of novel genes into existing regulatory gene networks (co-option), and less often through adaptive evolutionary processes in the coding portions of a gene. As a consequence, it is of great interest to examine whether the widespread conservation of the genetic machinery implies the same developmental function in a last common ancestor, or whether homologous genes acquired new developmental roles in structures of independent phylogenetic origin. To distinguish between these two possibilities one must refer to current concepts of phylogeny reconstruction and carefully investigate homology relationships. Particularly problematic in terms of homology decisions is the use of gene expression patterns of a given structure. In the future, research on more organisms other than the typical model systems will be required since these can provide insights that are not easily obtained from comparisons among only a few distantly related model species

Fgfr1 signalling in the development of a sexually selected trait in vertebrates, the sword of swordtail fish

<p>Abstract</p> <p>Background</p> <p>One of Darwin's chosen examples for his idea of sexual selection through female choice was the "sword", a colourful extension of the caudal fin of male swordtails of the genus <it>Xiphophorus</it>. Platyfish, also members of the genus <it>Xiphophorus</it>, are thought to have arisen from within the swordtails, but have secondarily lost the ability to develop a sword. The sustained increase of testosterone during sexual maturation initiates sword development in male swordtails. Addition of testosterone also induces sword-like fin extensions in some platyfish species, suggesting that the genetic interactions required for sword development may be dormant, rather than lost, within platyfish. Despite considerable interest in the evolution of the sword from a behavioural or evolutionary point of view, little is known about the developmental changes that resulted in the gain and secondary loss of the sword. Up-regulation of <it>msxC </it>had been shown to characterize the development of both swords and the gonopodium, a modified anal fin that serves as an intromittent organ, and prompted investigations of the regulatory mechanisms that control <it>msxC </it>and sword growth.</p> <p>Results</p> <p>By comparing both development and regeneration of caudal fins in swordtails and platyfish, we show that <it>fgfr1 </it>is strongly up-regulated in developing and regenerating sword and gonopodial rays. Characterization of the fin overgrowth mutant <it>brushtail </it>in a platyfish background confirmed that fin regeneration rates are correlated with the expression levels of <it>fgfr1 </it>and <it>msxC</it>. Moreover, <it>brushtail </it>re-awakens the dormant mechanisms of sword development in platyfish and activates <it>fgfr1/msxC</it>-signalling. Although both genes are co-expressed in scleroblasts, expression of <it>msxC </it>in the distal blastema may be independent of <it>fgfr1</it>. Known regulators of Fgf-signalling in teleost fins, <it>fgf20a </it>and <it>fgf24</it>, are transiently expressed only during regeneration and thus not likely to be required in developing swords.</p> <p>Conclusion</p> <p>Our data suggest that Fgf-signalling is involved upstream of <it>msxC </it>in the development of the sword and gonopodium in male swordtails. Activation of a gene regulatory network that includes <it>fgfr1 </it>and <it>msxC </it>is positively correlated with fin ray growth rates and can be re-activated in platyfish to form small sword-like fin extensions. These findings point towards a disruption between the <it>fgfr1/msxC </it>network and its regulation by testosterone as a likely developmental cause for sword-loss in platyfish.</p

The origin of bmp16, a novel Bmp2/4 relative, retained in teleost fish genomes

<p>Abstract</p> <p>Background</p> <p>Whole genome sequences have allowed us to have an overview of the evolution of gene repertoires. The target of the present study, the TGFβ superfamily, contains many genes involved in vertebrate development, and provides an ideal system to explore the relationships between evolution of gene repertoires and that of developmental programs.</p> <p>Results</p> <p>As a result of a bioinformatic survey of sequenced vertebrate genomes, we identified an uncharacterized member of the TGFβ superfamily, designated <it>bmp16</it>, which is confined to teleost fish species. Our molecular phylogenetic study revealed a high affinity of <it>bmp16 </it>to the <it>Bmp2/4 </it>subfamily. Importantly, further analyses based on the maximum-likelihood method unambiguously ruled out the possibility that this teleost-specific gene is a product of teleost-specific genome duplication. This suggests that the absence of a <it>bmp16 </it>ortholog in tetrapods is due to a secondary loss. <it>In situ </it>hybridization showed embryonic expression of the zebrafish <it>bmp16 </it>in the developing swim bladder, heart, tail bud, and ectoderm of pectoral and median fin folds in pharyngula stages, as well as gut-associated expression in 5-day embryos.</p> <p>Conclusion</p> <p>Comparisons of expression patterns revealed (1) the redundancy of <it>bmp16 </it>expression with its homologs in presumably plesiomorphic expression domains, such as the fin fold, heart, and tail bud, which might have permitted its loss in the tetrapod lineage, and (2) the loss of craniofacial expression and gain of swim bladder expression of <it>bmp16 </it>after the gene duplication between <it>Bmp2</it>, <it>-4 </it>and <it>-16</it>. Our findings highlight the importance of documenting secondary changes of gene repertoires and expression patterns in other gene families.</p

Retinoic Acid Is Involved in the Metamorphosis of the Anal Fin into an Intromittent Organ, the Gonopodium, in the Green Swordtail (Xiphophorus hellerii)

In poeciliid fish the male anal fin has been transformed into a gonopodium, an intromittent organ required for internal fertilization. Elevated testosterone levels induce metamorphosis of a subset of anal fin rays to grow and form the specialized terminal structures of the gonopodium. The molecular mechanisms underlying these processes are largely unknown. Here, we investigated whether retinoic acid (RA) signaling is involved in gonopodium development in the swordtail Xiphophorus hellerii. We showed that aldh1a2, a RA synthesizing enzyme, and the RA receptors, rar-ga and rar-gb, are expressed in anal fins during metamorphosis. aldh1a2 expression is regulated by testosterone in a concentration-dependent manner and is up-regulated in both hormone-induced and naturally developing gonopodia. Androgen receptor (ar), a putative regulator of gonopodial development, is co-expressed with aldh1a2 and the RA receptors in gonopodial rays. Importantly, experimental increase of RA signaling promoted growth of the gonopodium and increased the number of new segments. Based on gene expression analyses and pharmacological manipulation of gonopodium development, we show that the RA signaling pathway is activated in response to androgen signaling and promotes fin ray growth and development during the metamorphosis of the anal fin into the gonopodium

2-Amino-4-aryl-5-oxo-4,5-dihydropyrano[3,2-c]chromene-3-carbonitriles with Microtubule-Disruptive, Centrosome-Declustering, and Antiangiogenic Effects in vitro and in vivo

A series of fifteen 2‐amino‐4‐aryl‐5‐oxo‐4,5‐dihydropyrano[3,2‐c]chromene‐3‐carbonitriles (1 a–o) were synthesized via a three‐component reaction of 4‐hydroxycoumarin, malononitrile, and diversely substituted benzaldehydes or pyridine carbaldehydes. The compounds were tested for anticancer activities against a panel of eight human tumor cell lines. A few derivatives with high antiproliferative activities and different cancer cell specificity were identified and investigated for their modes of action. They led to microtubule disruption, centrosome de‐clustering and G2/M cell cycle arrest in 518 A2 melanoma cells. They also showed anti‐angiogenic effects in vitro and in vivo

Hindbrain patterning revisited : timing and effects of retinoic acid signalling

Retinoids play a critical role in patterning, segmentation, and neurogenesis of the posterior hindbrain and it has been proposed that they act as a posteriorising signal during hindbrain development. Until now, direct evidence that endogenous retinoid signalling acts through a gradient to specify cell fates along the anteroposterior axis has been missing. Two recent studies tested the requirement for retinoid signalling in the developing hindbrain through systematic application of a panretinoic acid receptor antagonist.(1,2) They demonstrate a stage-dependent requirement for increasing retinoid signalling activity along the hindbrain that proceeds from anterior to posterior. Together these findings challenge the concept of a stable gradient of retinoic acid across the hindbrain and warrant a re-interpretation of the phenotypes obtained by genetic and nutritional disruption of retinoid signalling in the amniote embryo

An organizer controls the development of the "sword" : a sexually selected trait in swordtail fish

Male swordtail fish of the genus Xiphophorus (Poeciliidae) possess a "sword" that is composed of several colored elongated ventral fin rays of the caudal fin. The sword is a secondary sexual trait that evolved through sexual selection by female preference. To uncover the developmental mechanisms underlying the metamorphosis from a juvenile caudal fin to the sword, we have devised a transplantation protocol to assay the fate of single transplanted fin rays and their interactions with flanking rays. These experiments provide evidence for the existence of a previously unrecognized inductive signal that originates in those rays that develop into the two longest sword rays. This "sword organizer" causes adjacent fin rays to grow and become integrated into the sword and induces the development of an additional, typically pigmented sword in grafts to the dorsal part of the caudal fin. We show that the potential to develop a sword is restricted to certain parts of the caudal fin. Our findings suggest that the evolution of swords in swordtails required the acquisition of two developmental mechanisms: the establishment of signaling competence in prospective sword rays in the embryo or early larva, and its activation through androgen signaling in adult male fish