In vertebrates it is often found that if one considers a group of genes clustered on a certain chromosome, then the homologues of those genes often form another cluster on a different chromosome. There are four explanations, not necessarily mutually exclusive, to explain how such homologous clusters appeared. Homologous clusters are expected at a low probability even if genes are distributed at random. The duplication of a subset of the genome might create homologous clusters, as would a duplication of (...) the entire genome. Alternatively, it may be adaptive for certain combinations of genes to cluster, although clearly the genes must have duplicated prior to rearrangement into clusters. Molecular phylogenetics provides a means to examine the origins of homologous clusters, although it is difficult to discriminate between the different explanations using current data. However, with more extensive sequencing and mapping of vertebrate genomes, especially those of the early diverging chordates, it should soon become possible to resolve the origins of homologous clusters. BioEssays 21:697–703, 1999. © 1999 John Wiley & Sons, Inc. (shrink)

The potential of the vertebrate limb as a model system to study developmental mechanisms is particularly well illustrated by the analysis of the Hox gene network. These genes are probably involved in the establishment of patterns encoding positional information. Their functional organisation during both limb and trunk development are very similar and seem to involve the progressive activation in time, along the chromosome, of a battery of genes whose products could differentially instruct those cells where they are expressed. This process (...) may be common to all organisms that develop according to an anterior‐posterior morphogenetic progression. The possible linkage of this system to a particular mechanism of segmentation as well as its phylogenetic implications are discussed. (shrink)

The potential of the vertebrate limb as a model system to study developmental mechanisms is particularly well illustrated by the analysis of the Hox gene network. These genes are probably involved in the establishment of patterns encoding positional information. Their functional organisation during both limb and trunk development are very similar and seem to involve the progressive activation in time, along the chromosome, of a battery of genes whose products could differentially instruct those cells where they are expressed. This process (...) may be common to all organisms that develop according to an anterior‐posterior morphogenetic progression. The possible linkage of this system to a particular mechanism of segmentation as well as its phylogenetic implications are discussed. (shrink)

Hindbrain development is orchestrated by a vertebrate gene regulatory network that generates segmental patterning along the anterior–posterior axis via Hox genes. Here, we review analyses of vertebrate and invertebrate chordate models that inform upon the evolutionary origin and diversification of this network. Evidence from the sea lamprey reveals that the hindbrain regulatory network generates rhombomeric compartments with segmental Hox expression and an underlying Hox code. We infer that this basal feature was present in ancestral vertebrates and, as an evolutionarily (...) constrained developmental state, is fundamentally important for patterning of the vertebrate hindbrain across diverse lineages. Despite the common ground plan, vertebrates exhibit neuroanatomical diversity in lineage‐specific patterns, with different vertebrates revealing variations of Hox expression in the hindbrain that could underlie this diversification. Invertebrate chordates lack hindbrain segmentation but exhibit some conserved aspects of this network, with retinoic acid signaling playing a role in establishing nested domains of Hox expression. (shrink)

Teeth are one of the most fascinating innovations of vertebrates. Their diversity of shape, size, location, and number in vertebrates is astonishing. If the molecular mechanisms underlying the morphogenesis of individual teeth are now relatively well understood, thanks to the detailed experimental work that has been performed in model organisms (mainly mouse and zebrafish), the mechanisms that control the organization of the dentition are still a mystery. Mammals display simplified dentitions when compared to other vertebrates with only (...) a single tooth row positioned in the anterior part of the mouth, whereas other vertebrates exhibit tooth rows in many locations. As proposed 60 years ago, tooth rows can be formed sequentially from an initiator tooth. Recent results in zebrafish have now largely confirmed this hypothesis. Here this observation is generalized upon and it is suggested that in most vertebrates tooth rows could form sequentially from a single initiator tooth. (shrink)

In vertebrates the antero‐posterior organization of the embryonic body axis is thought to result from the activity of two separate centers, the head organizer and the trunk organizer, as operationally defined by Spemann in the 1920s. Current molecular studies have supported the existence of a trunk organizer activity while the presence of a distinct head inducing center has remained elusive. Mainly based on analyses of headless mutants in mice, it has been proposed that the anterior axial mesoderm plays a (...) determining role in head induction. Recent gain‐ and loss‐of‐function studies in various organisms, however, provide compelling evidence that a largely ignored region, the anterior primitive endoderm, specifies rostral identity. In this review we discuss the emerging concept that the anterior primitive endoderm, rather than the prechordal plate mesoderm, induces head development in the vertebrate embryo. (shrink)

Two embryonic tissues—the neural crest and the cranial placodes—give rise to most evolutionary novelties of the vertebrate head. These two tissues develop similarly in several respects: they originate from ectoderm at the neural plate border, give rise to migratory cells and develop into multiple cell fates including sensory neurons. These similarities, and the joint appearance of both tissues in the vertebrate lineage, may point to a common evolutionary origin of neural crest and placodes from a specialized population of neural plate (...) border cells. However, a review of the developmental mechanisms underlying the induction, specification, migration and cytodifferentiation of neural crest and placodes reveals fundamental differences between the tissues. Taken together with insights from recent studies in tunicates and amphioxus, this suggests that neural crest and placodes have an independent evolutionary origin and that they evolved from the neural and non‐neural side of the neural plate border, respectively. BioEssays 30:659–672, 2008. © 2008 Wiley Periodicals, Inc. (shrink)

Many biologists assume, as Darwin did, that natural selection acts mainly on late embryonic or postnatal development. This view is consistent with von Baer's observations of morphological divergence at late stages. It is also suggested by the conserved morphology and common molecular genetic mechanisms of pattern formation seen in embryos. I argue here, however, that differences in adult morphology may be generated at a variety of stages. Natural selection may have a major action on developmental mechanisms during the organogenetic period, (...) because this is when many adult traits are specified. Evolutionary changes in these early developmental mechanisms probably include subtle shifts in the timing of gene expression. Changes of this kind have little or no gross effect on the anatomy of the embryo; they are only phenotypically expressed, or readily detected, when amplified at later stages. The phylotypic stage, the developmental hourglass, modularity, and von Baerian divergence are reassessed in terms of these arguments. BioEssays 21:604–613, 1999. © 1999 John Wiley & Sons, Inc. (shrink)

At the end of the nineteenth century, Ludwig Edinger completed the first comparative survey of the microscopic anatomy of vertebrate brains. He is regarded as the founder of the field of comparative neuroanatomy. Modern commentators have misunderstood him to have espoused an anti-Darwinian linear view of brain evolution, harkening to the metaphysics of the scala naturae. This understanding arises, in part, from an increasingly contested view of nineteenth-century morphology in Germany. Edinger did espouse a progressionist, though not strictly linear, view (...) of forebrain evolution, but his work also provided carefully documented evidence that brain stem structures vary in complexity independently from one another and across species in a manner that is not compatible with linear progress. This led Edinger to reject progressionism for all brain structures other than the forebrain roof, based on reasoning not too dissimilar from those his successors used to dismiss it for the forebrain roof. (shrink)

All surviving jawed vertebrate representatives achieve diversity in immunoglobulin‐based B and T cell receptors for antigen recognition through recombinatorial rearrangement of V(D)J segments. However, the extant jawless vertebrates, lampreys and hagfish, instead generate three types of variable lymphocyte receptors (VLRs) through a template‐mediated combinatorial assembly of different leucine‐rich repeat (LRR) sequences. The clonally diverse VLRB receptors are expressed by B‐like lymphocytes, while the VLRA and VLRC receptors are expressed by lymphocyte lineages that resemble αβ and γδ T lymphocytes, respectively. (...) These findings suggest that three basic types of lymphocytes, one B‐like and two T‐like, are an essential feature of vertebrate adaptive immunity. Around 500 million years ago, a common ancestor of jawed and jawless vertebrates evolved a genetic program for the development of prototypic lymphoid cells as a foundation for an adaptive immune system. This acquisition preceded the convergent evolution of alternative types of clonally diverse receptors for antigens in all vertebrates, as reviewed in this article. (shrink)

Knowledge of the structure of ancestral genomes provides the basis of a new framework to better represent and interpret results from genomic and evolutionary studies. Because these ancestors lived tens of hundreds of million years ago, this knowledge will inevitably take the form of abstract representations, reconstructed on the basis both of experimental evidence collected on extant genomes and of our understanding of evolutionary processes. This is the field of Paleogenomics, a young discipline that is providing an increasingly precise picture (...) of our ancestral vertebrate genomes based on cytogenetic data, genome sequences and new algorithmic developments. Many recent studies have focused on the ancestral placental mammal and teleost fish genomes, although the outlines of even more distant pre‐vertebrate ancestors are being reported. BioEssays 30:122–134, 2008. © 2008 Wiley Periodicals, Inc. (shrink)

The ontogeny of the vertebrate retina has been a topic of interest to developmental biologists and human geneticists for many decades. Understanding the unfolding of the genetic program that transforms a field of progenitors cells into a functionally complex and multi‐layered sensory organ is a formidable challenge. Although classical genetic studies succeeded in identifying the key regulators of retina specification, understanding the architecture of their gene network and predicting their behavior are still a distant hope. The emergence of next‐generation sequencing (...) platforms revolutionized the field unlocking the access to genome‐wide datasets. Emerging techniques such as RNA‐seq, ChIP‐seq, ATAC‐seq, or single cell RNA‐seq are used to characterize eye developmental programs. These studies provide valuable information on the transcriptional and cis‐regulatory profiles of precursors and differentiated cells, outlining the trajectories that connect each intermediate state. Here, recent systems biology efforts are reviewed to understand the genetic programs shaping the vertebrate retina. (shrink)

What initiates vertebrate limb development and induces limbs to form where they do? For several years the answer to this intriguing question has been framed in terms of a working model that limb induction depends on a dialogue between two members of the Fibroblast Growth Factor (FGF) family of intercellular signaling molecules, FGF8 and FGF10. Now, a recent paper has written roles for signals encoded by WNT genes, the vertebrate relatives of the Drosophila wingless gene, into the script.(1) BioEssays 23:865–868, (...) 2001. © 2001 John Wiley & Sons, Inc. (shrink)

The development of the vertebrate skeleton is under complex genetic control, and good progress is being made towards identifying the genes responsible. A recent paper(1) contributes to this progress by describing transgenic mice in which the homeobox‐containing MHox gene has been disrupted. MHox(−/−) mice have a range of skeletal defects, involving loss or shortening of structures in the skull, face and limb. Puzzling features of the MHox(−/−) mutation, which has similar effects on bones with very different embryological origins and yet (...) spares other bones completely, may hold clues to the mechanisms that shape the skeleton. MHox(−/−) mice, used in conjunction with other skeletal mutants, will be important tools for exploring these mechanisms further. (shrink)

The evolutionary history of muscle development in the paired fins of teleost fish and the limbs of tetrapod vertebrates is still, to a large extent, uncertain. There has been a consensus, however, that in the vertebrate clade the ancestral mechanism of fin and limb muscle development involves the extension of epithelial tissues from the somite into the fin/limb bud. This mechanism has been documented in chondrichthyan, dipnoan, chondrostean and teleost fishes. It has also been assumed that in amniotes, in (...) contrast, individual progenitor cells of muscles migrate from the somites into the limb buds. Neyt et al.(1) now present the exciting finding that in zebrafishes this presumably derived mechanism involving individual cell migration, is present. They conclude, based on data on sharks, zebrafishes, chickens, quails and mice that the derived mechanism was present in the sarcopterygians. This conclusion, however, may be premature in the light of further data available in the literature, which show a highly mosaic distribution of this character in the vertebrate clade. Furthermore, a developmental mode exists that is intermediate between the supposed ancestral and derived modes in teleosts, reptiles and possibly amphibians. BioEssays 23:383–387, 2001. © 2001 John Wiley & Sons, Inc. (shrink)

Biological boundaries are important because of what they reveal about the evolution of a lineage, the relationship between organisms of different lineages, the structure and function of particular subsystems of the organism, the interconnection between an organism and its environment, and a myriad of other important issues related to individuality, development, and evolution. Since there is no single unifying theory for all biological sciences, there are various possible theoretical characterizations of what counts as a biological boundary. Theoretical specificity is crucial (...) for the full characterization of a boundary; to this end, it is useful to begin with general properties and then to compare these to those properties specific to a particular biological boundary. This dual heuristic approach—top-down and bottom-up—can then be repeated to increase the robustness of the boundary characterization. In what follows, I explore both the general structural and functional aspects of biological boundaries and those specific to a biological subsystem, which itself is critical to boundary formation, maintenance, and evolution—the vertebrate immune system. It is a remarkable and sobering regularity of nature that organisms remain whole because their parts are constantly being built up and broken down, and this is no less true of their boundaries. The vertebrate immune system is at the center of this process of biological boundary maintenance and breakdown. (shrink)

One of the most remarkable recent findings in developmental biology has been the colinear and homologous relationships shared between the Drosophila HOM‐C and vertebrate Hox homeobox gene complexes. These relationships pose the question of the functional significance of colinearity and its molecular basis. While there was much initial resistance to the validity of this comparison, it now appears the Hox/HOM homology reflects a broad degree of evolutionary conservation which has reawakened interest in comparative embryology and evolution.The evolutionary conservation of protein (...) motifs in many gene families (including those for growth factors, secreted and membrane bound signalling factors, adhesion molecules, cytoplasmic receptor kinases, nuclear receptors and transcription factors) has lead to speculation on the extent to which these homology relationships represent common developmental processes and underlying molecular mechanisms. Structural identities in a protein may indicate the biochemical/molecular function that a protein plays in cellular and developmental processes, without reflecting a conserved role in a cascade of developmental events. However, the analysis of genes encoding transcription factors has provided evidence suggesting that there are gene complexes in arthropods and vertebrates which are true homologues and which may share common roles in the specification of regional identity along embryonic A‐P axis. These genes comprise the Box/HOM‐C homeotic complexes. This review will detail some of the evidence for this proposed relationship and will speculate on the functional implications. (shrink)

Although most aspects of world and self-consciousness are inherently subjective, neuroscience studies in humans and non-human animals provide correlational and causative indices of specific links between brain activity and representation of the self and the world. In this article we review neuroanatomic, neurophysiological and neuropsychological data supporting the hypothesis that different levels of self and world representation in vertebrates rely upon i) a 'basal' subcortical system that includes brainstem, hypothalamus and central thalamic nuclei and that may underpin the primary (...) (or anoetic) consciousness likely present in all vertebrates; and ii) a forebrain system that include the medial and lateral structures of the cerebral hemispheres and may sustain the most sophisticated forms of consciousness (e.g. noetic (knowledge based) and autonoetic, reflective knowledge). We posit a mutual, bidirectional functional influence between these two major brain circuits. We conclude that basic aspects of consciousness like primary self and core self (based on anoetic and noetic consciousness) are present in many species of vertebrates and that, even self-consciousness (autonoetic consciousness) does not seem to be a prerogative of humans and of some non-human primates but may, to a certain extent, be present in some other mammals and birds. (shrink)

Adaptive immunity is unique to the vertebrates, and the molecules involved (including immunoglobulins, T cell receptors and the major histocompatibility complex molecules) seem to have diversified very rapidly early in vertebrate history. Reconstruction of gene phylogenies has yielded insights into the evolutionary origin of a number of molecular systems, including the complement system and the major histocompatibility complex (MHC). These analyses have indicated that the C5 component of complement arose by gene duplication prior to the divergence of C3 and (...) C4, which suggests that the alternative complement pathway was the first to evolve. In the case of the MHC, phylogenetic analysis supports the hypothesis that MHC class II molecules evolved before class I molecules. The fact that the MHC‐linked proteasome components that specifically produce peptides for presentation by class I MHC appear to have originated before the separation of jawed and jawless vertebrates suggests that the MHC itself may have been present at this time. Immmune system gene families have evolved by gene duplication, interlocus recombination and (in some cases) positive Darwinian selection favoring diversity at the amino acid level. (shrink)

Recoverin is a 23 kDa Ca2+binding protein that has been detected primarily in vertebrate photoreceptors. The role of recoverin in phototransduction has been investigated using a variety of biochemical methods. Initial reports suggesting that recoverin regulates photoreceptor guanylyl cyclase have not been confirmed. Instead, recoverin appears to determine the lifetime of lightstimulated phosphodiesterase activity, perhaps by regulating rhodopsin phosphorylation. Retinal recoverin is heterogeneously fatty acylated at its ammo-terminus. The amino-terminal fatty acid appears to be involved in the interaction of recoverin (...) with photoreceptor membranes. (shrink)

I propose that a dishonest signaling system can be evolutionarily stable in eusocial animal societies if the amount of dishonesty is balanced by the chance of non-reproductive workers to advance to the reproductive caste in the future. I express this trade-off in a modified form of Hamilton’s rule, where I distinguish between the real and perceived cost of an altruistic act, and between the real and perceived genetic relatedness between colony members. Furthermore, I elaborate how the vertebrate neuromodulator oxytocin could (...) serve as an internal representation of the perceived cost of an altruistic act and of perceived relatedness. Behavioral and receptor localization data support this hypothesis. The encoding of cost and relatedness by oxytocin is likely integrated with a number of other functions related to social bonding. I conclude with a discussion of honesty in signaling, an outline of testable consequences of this hypothesis, and a comparison between vertebrate and insect eusociality. (shrink)

The mouthparts of anuran tadpoles are highly derived compared to those of caecilians or salamanders. The suprarostral cartilages support the tadpole's upper beak; the infrarostral cartilages support the lower beak. Both supra‐ and infrarostral cartilages are absent in other vertebrates. These differences reflect the evolutionary origin of a derived feeding mode in anuran tadpoles. We suggest that these unique cartilages stem from the evolution of new articulations within preexisting cartilages, rather than novel cartilage condensations. We propose testing this hypothesis (...) through a search for similarities in the development of the suprarostral and infrarostral cartilage articulations and of the primary jaw joint. In Xenopus, the gene zax is expressed in a region corresponding to the infrarostral cartilage. This gene is related to the bapx1‐gene, which regulates jaw joint development. Further investigation of these genes, as well as other genes with joint‐related functions, in anuran craniofacial development may provide a connection between the morphological diversity seen in the vertebrate head and the corresponding diversity in genetic regulatory processes. We believe that the evolution of larval jaws in anurans may shed light on the general evolutionary mechanisms of how new articulations, not only in the jaw region, could have arisen in the vertebrate skull. BioEssays 27: 526–532, 2005. © 2005 Wiley periodicals, Inc. (shrink)

The idea that concentration gradients of crucial substances might control the pattern of development, even in the embryos of complex organisms, has been around for a long time, but mostly in obscure forms. Twenty five years ago clear, experimentally testable ideas about how such gradients might work were enunciated, and more recently the morphogen gradient principle was shown to underlie the beginnings of patterning in Drosophila. Is it also central to vertebrate development? Four recent papers raise experimentation to a new (...) level(1–4), while showing how difficult it might be to pin down the precise form of the mechanism. (shrink)

Embryonic development results in animals whose body plans exhibit a variety of symmetry types. While significant progress has been made in understanding the molecular events underlying the early specification of the antero‐posterior and dorso‐ventral axes, little information has been available regarding the basis for left‐right (LR) differences in animal morphogenesis. Recently however, important advances have been made in uncovering the molecular mechanisms responsible for LR patterning. A number of genes (including well‐known signaling molecules such as Sonic hedgehog and activin) are (...) asymmetrically expressed in early chick embryos, well before the appearance of morphological asymmetries. One of these, nodal, is asymmetrically expressed in frogs and mice as well, and its expression is altered in mouse mutants exhibiting defects in laterality. In the chick, these genes regulate each other in a sequential cascade, which independently determines the situs of the heart and other organs. (shrink)

Embryonic development results in animals whose body plans exhibit a variety of symmetry types. While significant progress has been made in understanding the molecular events underlying the early specification of the antero‐posterior and dorso‐ventral axes, little information has been available regarding the basis for left‐right (LR) differences in animal morphogenesis. Recently however, important advances have been made in uncovering the molecular mechanisms responsible for LR patterning. A number of genes (including well‐known signaling molecules such as Sonic hedgehog and activin) are (...) asymmetrically expressed in early chick embryos, well before the appearance of morphological asymmetries. One of these, nodal, is asymmetrically expressed in frogs and mice as well, and its expression is altered in mouse mutants exhibiting defects in laterality. In the chick, these genes regulate each other in a sequential cascade, which independently determines the situs of the heart and other organs. (shrink)

Skeletal myoblasts have their origin early in embryogenesis within specific somites. Determined myoblasts are committed to a myogenic fate; however, they only differentiate and express a muscle‐specific phenotype after they have received the appropriate environmental signals. Once proliferating myoblasts enter the differentiation programme they withdraw from the cell cycle and form post‐mitotic multinucleated myofibres (myogenesis); this transformation is accompanied by muscle‐specific gene expression. Muscle development is associated with complex and diverse protein isoform transitions, generated by differential gene expression and mRNA (...) splicing. The myofibres are in a state of dynamic adaptation in response to hormones, mechanical activity and motor innervation, which modulate differential gene expression and splicing during this functional acclimatisation. This review will focus on the profound effects of thyroid hormone on skeletal muscle, which produce alterations in gene and isoform expression, biochemical properties and morphological features that precipitate in modified contractile/mechanical characteristics. Insight into the molecular events that control these events was provided by the recent characterisation of the MyoD gene family, which encodes helix‐loop‐helix proteins; these activate muscle‐specific transcription and serve as targets for a variety of physiological stimuli. The current hypothesis on hormonal regulation of myogenesis is that thyroid hormones (1) directly regulate the myoD and contractile protein gene families, and (2) induce thyroid hormone receptor‐transcription factor interactions critical to gene expression. (shrink)

We recently examined gene expression during Xenopus tadpole tail appendage regeneration and found that carbohydrate regulatory genes were dramatically altered during the regeneration process. In this essay, we speculate that these changes in gene expression play an essential role during regeneration by stimulating the anabolic pathways required for the reconstruction of a new appendage. We hypothesize that during regeneration, cells use leptin, slc2a3, proinsulin, g6pd, hif1α expression, receptor tyrosine kinase (RTK) signaling, and the production of reactive oxygen species (ROS) to (...) promote glucose entry into glycolysis and the pentose phosphate pathway (PPP), thus stimulating macromolecular biosynthesis. We suggest that this metabolic shift is integral to the appendage regeneration program and that the Xenopus model is a powerful experimental system to further explore this phenomenon.Also watch the Video Abstract. (shrink)

Amphioxus represents the most basally divergent group in chordates and probably the best extant proxy to the ancestor of all chordates including vertebrates. The amphioxus, or lancelets, are benthic filter feeding marine animals and their interest as a model in research is due to their phylogenetic position and their anatomical and genetic stasis throughout their evolutionary history. From the first works in the 19th century to the present day, enormous progress is made mainly favored by technical development at different (...) levels, from spawning induction and husbandry techniques, through techniques for studies of gene function or of the role of different signalling pathways through embryonic development, to functional genomics techniques. Together, these advances foretell a plethora of interesting developments in the world of research with the amphioxus model. Here, the author review the discovery and development of amphioxus as a superb model organism in evolutionary and evolutionary‐developmental biology. (shrink)

Recent work on receptor molecules and cells used prototypical sweet, salty, sour, bitter, and umami stimuli. Labeled-line coding was supported, but it remains possible that the molecules and cells could respond to other tastants. Studies with other tastants are needed. The sensory message might contain two codes – one for attraction or aversion, the other, across-fiber patterning of stimulus quality.

This article reviews the recent reissuing of Richard Owen’s On the Nature of Limbs and its three novel, introductory essays. These essays make Owen’s 1849 text very accessible by discussing the historical context of his work and explaining how Owen’s ideas relate to his larger intellectual framework. In addition to the ways in which the essays point to Owen’s relevance for contemporary biology, I discuss how Owen’s unity of type theory and his homology claims about fins and limbs compare with (...) modern views. While the phenomena studied by Owen are nowadays of major interest to evolutionary developmental biology, research in evo-devo has largely shifted from homology (which was Owen’s concern) towards evolutionary novelty, e.g., accounting for fins as a novelty. Still, I argue that questions about homology are important and raise challenges even for explanations of novelty. (shrink)

A mechanism for the generation of the morphological left‐right asymmetry in higher organisms is proposed, based on the idea that chirality at the molecular level is the primordial source for macroscopic asymmetry. This mechanism accounts for a variety of experimental results on artificial production of situs inversus and fits well with mutations in mice causing visceral transposition.