Developmental Genetic Mechanisms Research Articles

Decoding the transcriptional basis for GABAergic interneuron diversity in the mouse neocortex

The locally projecting GABAergic interneurons of the mammalian cerebral cortex are a highly heterogeneous population, whose malfunction or deficit has been implicated in a wide range of neurological disorders. However, the low incidence of the various distinct interneuron populations within the neocortex, combined with the lack of molecular or physiological markers specific to these subtypes, have hampered investigations into their function in the normal and dysfunctional brain. A number of research groups have begun to elucidate the developmental genetic mechanism that underpins this diversity in the mouse neocortex, spurred on by the knowledge that the temporal and spatial origin of an interneuron in the embryonic brain is predictive of its eventual intrinsic properties in the mature cortex. In this review we highlight a number of recent findings that strengthen our understanding of the transcription factor code that is at the heart of generating this diversity. Further understanding of this code will enable selective observation, targeting and manipulation of interneuron subtypes across both in vitro and in vivo systems.

Notch/Delta signalling is not required for segment generation in the basally branching insectGryllus bimaculatus

Arthropods and vertebrates display a segmental body organisation along all or part of the anterior-posterior axis. Whether this reflects a shared, ancestral developmental genetic mechanism for segmentation is uncertain. In vertebrates, segments are formed sequentially by a segmentation 'clock' of oscillating gene expression involving Notch pathway components. Recent studies in spiders and basal insects have suggested that segmentation in these arthropods also involves Notch-based signalling. These observations have been interpreted as evidence for a shared, ancestral gene network for insect, arthropod and bilaterian segmentation. However, because this pathway can play multiple roles in development, elucidating the specific requirements for Notch signalling is important for understanding the ancestry of segmentation. Here we show that Delta, a ligand of the Notch pathway, is not required for segment formation in the cricket Gryllus bimaculatus, which retains ancestral characteristics of arthropod embryogenesis. Segment patterning genes are expressed before Delta in abdominal segments, and Delta expression does not oscillate in the pre-segmental region or in formed segments. Instead, Delta is required for neuroectoderm and mesectoderm formation; embryos missing these tissues are developmentally delayed and show defects in segment morphology but normal segment number. Thus, what initially appear to be 'segmentation phenotypes' can in fact be due to developmental delays and cell specification errors. Our data do not support an essential or ancestral role of Notch signalling in segment generation across the arthropods, and show that the pleiotropy of the Notch pathway can confound speculation on possible segmentation mechanisms in the last common bilaterian ancestor.

Codon usage patterns and adaptive evolution of marine unicellular cyanobacteria Synechococcus and Prochlorococcus

Marine unicellular cyanobacteria, represented by Synechococcus and Prochlorococcus, dominate the total phytoplankton biomass and production in oligotrophic ocean. In this study, we employed comparative genomics approaches to extensively investigate synonymous codon usage bias and evolutionary rates in a large number of closely related species of marine unicellular cyanobacteria. Although these two groups of marine cyanobacteria have a close phylogenetic relationship, we find that they are highly divergent not only in codon usage patterns but also in the driving forces behind the diversification. It is revealed that in Prochlorococcus, mutation and genome compositional constraints are the main forces contributing to codon usage bias, whereas in Synechococcus, translational selection. In addition, nucleotide substitution rate analysis indicates that they are not evolving at a constant rate after the divergence and that the average dN/dS values of core genes in Synechococcus are significantly higher than those in Prochlorococcus. Our evolutionary genomic analysis provides the first insight into codon usage, evolutionary genetic mechanisms and environmental adaptation of Synechococcus and Prochlorococcus after divergence.

Enhancer-adoption as a mechanism of human developmental disease

Disruption of the long-range cis-regulation of developmental gene expression is increasingly recognized as a cause of human disease. Here, we report a novel type of long-range cis-regulatory mutation, in which ectopic expression of a gene is driven by an enhancer that is not its own. We have termed this gain of regulatory information as "enhancer adoption." We mapped the breakpoints of a de novo 7q inversion in a child with features of a holoprosencephaly spectrum (HPES) disorder and severe upper limb syndactyly with lower limb synpolydactyly. The HPES plausibly results from the 7q36.3 breakpoint dislocating the sonic hedgehog (SHH) gene from enhancers that are known to drive expression in the early forebrain. However, the limb phenotype cannot be explained by loss of known SHH enhancers. The SHH transcription unit is relocated to 7q22.1, ∼190 kb 3' of a highly conserved noncoding element (HCNE2) within an intron of EMID2. We show that HCNE2 functions as a limb bud enhancer in mouse embryos and drives ectopic expression of Shh in vivo recapitulating the limb phenotype in the child. This developmental genetic mechanism may explain a proportion of the novel or unexplained phenotypes associated with balanced chromosome rearrangements.

Why ontogenetic homology criteria can be misleading: lessons from digit identity transformations

As the basis for comparative biology, correctly assigning character homology is critical. Yet, identifying homologous characters in practice is often challenging. Among the major roadblocks is that the mechanistic bases of character homology remain in question. Thus, investigators must rely on several independent lines of evidence (e.g., character anatomy, phylogenetic distribution, or embryological position); however, these distinct sources of evidence often lead to conflicting diagnoses of character homology. What is more, there is no consensus regarding the relative importance of distinct lines of evidence for determining character homology. Here, we review the difficulties that have hindered the search for the mechanistic bases of character identity, and relate these issues to a recently proposed mechanistic hypothesis of character identity--the Character Identity Network Hypothesis. Next, using two well-studied cases of homology conflict (i.e., avian and skink digit identity), we assess the utility of different lines of evidence in diagnosing homology. We conclude that, when comparing adult structures, because anatomical characters more closely reflect the actions of the developmental genetic mechanisms of character individuation they are more reliable than embryological homology criteria.

Evolutionary genetic mechanisms of aging

The review systematizes the evolutionary genetic approaches to the problem of aging, basing on the concepts of different reliabilities of separate biological processes and of balance between the reliabilities of these processes at a level that guarantees survival and reproduction in aggressive environment. The basic concepts of the Kirkwood’s disposable soma theory, according to which the viability potential is determined by a compromise in the allocation of the organism’s resources between reproduction and repair and maintenance of the soma are discussed. The basic concepts of the balance evolutionary genetic theory of aging are presented.

Darwin's Galápagos finches in modern biology

One of the classic examples of adaptive radiation under natural selection is the evolution of 15 closely related species of Darwin's finches (Passeriformes), whose primary diversity lies in the size and shape of their beaks. Since Charles Darwin and other members of the Beagle expedition collected these birds on the Galápagos Islands in 1835 and introduced them to science, they have been the subjects of intense research. Many biology textbooks use Darwin's finches to illustrate a variety of topics of evolutionary theory, such as speciation, natural selection and niche partitioning. Today, as this Theme Issue illustrates, Darwin's finches continue to be a very valuable source of biological discovery. Certain advantages of studying this group allow further breakthroughs in our understanding of changes in recent island biodiversity, mechanisms of speciation and hybridization, evolution of cognitive behaviours, principles of beak/jaw biomechanics as well as the underlying developmental genetic mechanisms in generating morphological diversity. Our objective was to bring together some of the key workers in the field of ecology and evolutionary biology who study Darwin's finches or whose studies were inspired by research on Darwin's finches. Insights provided by papers collected in this Theme Issue will be of interest to a wide audience.

Defining the limits of flowers: the challenge of distinguishing between the evolutionary products of simple versus compound strobili

Recent phylogenetic reconstructions suggest that axially condensed flower-like structures evolved iteratively in seed plants from either simple or compound strobili. The simple-strobilus model of flower evolution, widely applied to the angiosperm flower, interprets the inflorescence as a compound strobilus. The conifer cone and the gnetalean 'flower' are commonly interpreted as having evolved from a compound strobilus by extreme condensation and (at least in the case of male conifer cones) elimination of some structures present in the presumed ancestral compound strobilus. These two hypotheses have profoundly different implications for reconstructing the evolution of developmental genetic mechanisms in seed plants. If different flower-like structures evolved independently, there should intuitively be little commonality of patterning genes. However, reproductive units of some early-divergent angiosperms, including the extant genus Trithuria (Hydatellaceae) and the extinct genus Archaefructus (Archaefructaceae), apparently combine features considered typical of flowers and inflorescences. We re-evaluate several disparate strands of comparative data to explore whether flower-like structures could have arisen by co-option of flower-expressed patterning genes into independently evolved condensed inflorescences, or vice versa. We discuss the evolution of the inflorescence in both gymnosperms and angiosperms, emphasising the roles of heterotopy in dictating gender expression and heterochrony in permitting internodal compression.

Animal evolution during domestication: the domesticated fox as a model

We review the evolution of domestic animals, emphasizing the effect of the earliest steps of domestication on its course. Using the first domesticated species, the dog (Canis familiaris), for illustration, we describe the evolutionary peculiarities during the historical domestication, such as the high level and wide range of diversity. We suggest that the process of earliest domestication via unconscious and later conscious selection of human-defined behavioral traits may accelerate phenotypic variations. The review is based on the results of a long-term experiment designed to reproduce early mammalian domestication in the silver fox (Vulpes vulpes) selected for tameability or amenability to domestication. We describe changes in behavior, morphology and physiology that appeared in the fox during its selection for tameability, which were similar to those observed in the domestic dog. Based on the data of the fox experiment and survey of relevant data, we discuss the developmental, genetic and possible molecular genetic mechanisms underlying these changes. We ascribe the causative role in evolutionary transformation of domestic animals to the selection for behavior and to the neurospecific regulatory genes it affects.

An exploration of LEAFY expression in independent evolutionary origins of rosette flowering in Brassicaceae

Whereas most Brassicaceae produce flowers on an elongated inflorescence, a few lineages produce flowers directly from the vegetative rosette on elongated pedicels. Knowing the extent to which independent origins of rosette flowering involve the same developmental and genetic mechanisms could clarify the constraints acting on plant architectural evolution. Prior work in Idahoa, Ionopsidium, and Leavenworthia suggested that changes in the activity or expression of the flower meristem identity gene, LEAFY (LFY), played a role in all three origins of rosette flowering. Here we studied the developmental morphology of L. crassa and immunolocalization of LFY protein in Leavenworthia and Ionopsidium to further compare independent origins of rosette flowering. Leavenworthia crassa differs from Ionopsidium and Idahoa in producing ebracteate flowers. Flowers are, however, associated with "squamules," here interpreted as stipules of a cryptic bract. LFY was detected in L. crassa flower primordia but not in inflorescence meristems. In contrast, the rosette flowering Io. acaule accumulated LFY protein in the inflorescence meristem, whereas its inflorescence-flowering close relative, Io. prolongoi, did not. Thus, although different cases of rosette flowering likely entailed modifications of the same meristem identity program, distinct developmental genetic mechanisms appear to be involved in each case.

Origins of the other metazoan body plans: the evolution of larval forms

Bilaterian animal body plan origins are not solely about adult forms. Most animals have larvae with body plans, ontogenies and ecologies distinct from adults. There are two primary hypotheses for larval origins. The first hypothesis suggests that the first animals were small pelagic forms similar to modern larvae, with adult bilaterian body plans evolved subsequently. The second hypothesis suggests that adult bilaterian body plans evolved first and that larval body plans arose by interpolation of features into direct-developing ontogenies. The two hypotheses have different consequences for understanding parsimony in evolution of larvae and of developmental genetic mechanisms. If primitive metazoans were like modern larvae and distinct adult forms evolved independently, there should be little commonality of patterning genes among adult body plans. However, sharing of patterning genes is observed. If larvae arose by co-option of adult bilaterian-expressed genes into independently evolved larval forms, larvae may show morphological convergence, but with distinct patterning genes, and this is observed. Thus, comparative studies of gene expression support independent origins of larval features. Precambrian and Cambrian embryonic fossils are also consistent with direct development of the adult as being primitive, with planktonic larvae arising during the Cambrian. Larvae have continued to co-opt genes and evolve new features, allowing study of developmental evolution.

The evolutionary genetics of personality

Genetic influences on personality differences are ubiquitous, but their nature is not well understood. A theoretical framework might help, and can be provided by evolutionary genetics. We assess three evolutionary genetic mechanisms that could explain genetic variance in personality differences: selective neutrality, mutation‐selection balance, and balancing selection. Based on evolutionary genetic theory and empirical results from behaviour genetics and personality psychology, we conclude that selective neutrality is largely irrelevant, that mutation‐selection balance seems best at explaining genetic variance in intelligence, and that balancing selection by environmental heterogeneity seems best at explaining genetic variance in personality traits. We propose a general model of heritable personality differences that conceptualises intelligence as fitness components and personality traits as individual reaction norms of genotypes across environments, with different fitness consequences in different environmental niches. We also discuss the place of mental health in the model. This evolutionary genetic framework highlights the role of gene‐environment interactions in the study of personality, yields new insight into the person‐situation‐debate and the structure of personality, and has practical implications for both quantitative and molecular genetic studies of personality. Copyright © 2007 John Wiley & Sons, Ltd.

Zebrafish dentition in comparative context

Studies of the zebrafish (Danio rerio) promise to contribute much to an understanding of the developmental genetic mechanisms underlying diversification of the vertebrate dentition. Tooth development, structure, and replacement in the zebrafish largely reflect the primitive condition of jawed vertebrates, providing a basis for comparison with features of the more extensively studied mammalian dentition. A distinctive derived feature of the zebrafish dentition is restriction of teeth to a single pair of pharyngeal bones. Such reduction of the dentition, characteristic of the order Cypriniformes, has never been reversed, despite subsequent and extensive diversification of the group in numbers of species and variety of feeding modes. Studies of the developmental genetic mechanism of dentition reduction in the zebrafish suggest a potential explanation for irreversibility in that tooth loss seems to be associated with loss of developmental activators rather than gain of repressors. The zebrafish and other members of the family Cyprinidae exhibit species-specific numbers and arrangements of pharyngeal teeth, and extensive variation in tooth shape also occurs within the family. Mutant screens and experimental alteration of gene expression in the zebrafish are likely to yield variant tooth number and shape phenotypes that can be compared with those occurring naturally within the Cyprinidae. Such studies may reveal the relative contribution to trends in dental evolution of biases in the generation of variation and sorting of this variation by selection or drift.

Directional asymmetry of pelvic vestiges in threespine stickleback

Extensive reduction of the size and complexity of the pelvic skeleton (i.e., pelvic reduction) has evolved repeatedly in Gasterosteus aculeatus. Asymmetrical pelvic vestiges tend to be larger on the left side (i.e., left biased) in populations studied previously. Loss of Pitx1 expression is associated with pelvic reduction in G. aculeatus, and pelvic reduction maps to the Pitx1 locus. Pitx1 knockouts in mice have reduced hind limbs, but the left limb is larger. Thus left-biased directional asymmetry of stickleback pelvic vestiges may indicate the involvement of Pitx1 in pelvic reduction. We examined 6,356 specimens from 27 Cook Inlet populations of G. aculeatus with extensive pelvic reduction. Samples from 20 populations exhibit the left bias in asymmetrical pelvic vestiges expected if Pitx1 is involved, and three have a slight, non-significant left bias. However, samples from three populations have a significant right bias, and one large sample from another population has equal frequencies of specimens with larger vestiges on the left or right side. A sample of fossil threespine stickleback also has significantly left-biased pelvic vestiges. These results suggest that silencing of Pitx1 or the developmental pathway in which it functions in the pelvis is the usual cause of pelvic reduction in most Cook Inlet populations of G. aculeatu, and that it caused pelvic reduction at least 10 million years ago in a stickleback population. A different developmental genetic mechanism is implicated for three populations with right-biased pelvic vestiges and for the population without directional asymmetry.

A conserved supergene locus controls colour pattern diversity in Heliconius butterflies.

We studied whether similar developmental genetic mechanisms are involved in both convergent and divergent evolution. Mimetic insects are known for their diversity of patterns as well as their remarkable evolutionary convergence, and they have played an important role in controversies over the respective roles of selection and constraints in adaptive evolution. Here we contrast three butterfly species, all classic examples of Müllerian mimicry. We used a genetic linkage map to show that a locus, Yb, which controls the presence of a yellow band in geographic races of Heliconius melpomene, maps precisely to the same location as the locus Cr, which has very similar phenotypic effects in its co-mimic H. erato. Furthermore, the same genomic location acts as a “supergene”, determining multiple sympatric morphs in a third species, H. numata. H. numata is a species with a very different phenotypic appearance, whose many forms mimic different unrelated ithomiine butterflies in the genus Melinaea. Other unlinked colour pattern loci map to a homologous linkage group in the co-mimics H. melpomene and H. erato, but they are not involved in mimetic polymorphism in H. numata. Hence, a single region from the multilocus colour pattern architecture of H. melpomene and H. erato appears to have gained control of the entire wing-pattern variability in H. numata, presumably as a result of selection for mimetic “supergene” polymorphism without intermediates. Although we cannot at this stage confirm the homology of the loci segregating in the three species, our results imply that a conserved yet relatively unconstrained mechanism underlying pattern switching can affect mimicry in radically different ways. We also show that adaptive evolution, both convergent and diversifying, can occur by the repeated involvement of the same genomic regions.

Developmental genetic mechanisms of evolutionary tooth loss in cypriniform fishes

The fossil record indicates that cypriniform fishes, a group including the zebrafish, lost oral teeth over 50 million years ago. Despite subsequent diversification of feeding modes, no cypriniform has regained oral teeth, suggesting the zebrafish as a model for studying the developmental genetic basis of evolutionary constraint. To investigate the mechanism of cypriniform tooth loss, we compared the oral expression of seven genes whose mammalian orthologs are involved in tooth initiation in the zebrafish and the Mexican tetra, Astyanax mexicanus, a related species retaining oral teeth. The most significant difference we found was an absence in zebrafish oral epithelium of expression of dlx2a and dlx2b, transcription factors that are expressed in early Astyanax odontogenic epithelium. Analysis of orthologous genes in the Japanese medaka (Oryzias latipes) and a catfish (Synodontis multipunctatus) suggests that expression was lost in cypriniforms, rather than gained in Astyanax. Treatment of Astyanax with an inhibitor of Fibroblast growth factor (Fgf) signaling produced a partial phenocopy of the zebrafish oral region, in that oral teeth, and expression of dlx2a and dlx2b, were lost, whereas shh and pitx2, genes whose expression is present in zebrafish oral epithelium, were unaffected. We hypothesize that a loss of Fgf signaling to oral epithelium was associated with cypriniform tooth loss.

Are Cirripedia hopeful monsters? Cytogenetic approach and evidence for a Hox gene cluster in the cirripede crustacean Sacculina carcini

The "hopeful monster" has haunted evolutionary thinking since Richard Goldschmidt coined the phrase in 1933. The phrase is directly related to genetic mechanisms in development and evolution. Cirripedes are peculiar crustaceans in that they all lack abdomens as adults. In a previous study aimed at describing the repertoire of Hox genes of the Cirripedia, we failed to isolate the abdominal-A gene in three species representative of all three cirripede orders. To address the question of whether the cirripede ancestor could have been a "hopeful monster" arising from a rearrangement of the Hox complex, we have performed a cytogenetic analysis of the Hox complex of the cirripede Sacculina carcini. We present here molecular and cytogenetic evidence for the grouping of the Hox genes on a single chromosome. This is the first direct evidence reported for the grouping of Hox genes on the same chromosome in a non-insect arthropod species.

Novel Genetic Mechanisms in Development

Novel Genetic Mechanisms in Development

Genetic Structure and Evolutionary History of a Diploid Hybrid Pine Pinus densata Inferred from the Nucleotide Variation at Seven Gene Loci

Although homoploid hybridization is increasingly recognized as an important phenomenon in plant evolution, its evolutionary genetic mechanisms are poorly documented and understood. Pinus densata, a pine native to the Tibetan Plateau, represents a good example of a homoploid hybrid speciation facilitated by adaptation to extreme environment and ecological isolation from the parents. Its ecologically and reproductively stabilized nature offers excellent opportunity for studying genetic processes associated with hybrid speciation. In this study, we investigated the levels and patterns of nucleotide variation in P. densata and its putative parents. Haplotype composition, gene genealogies, and the levels and patterns of nucleotide variation gave further support to the hybrid nature of P. densata. Allelic history, as revealed by our data, suggests the ancient nature of the hybrid preceding elevation of the Tibetan Plateau. We detected more deviations from neutrality in P. densata than in the parental species. Thus, at least some of the evolutionary forces that have shaped the genetic variation in P. densata are likely to be different from those acting upon parental species. We speculate that when populations of P. densata invaded new territories, they had elevated rates of response to selection in order to develop traits that help them to survive and adapt in the new environments.

The developing limb and the control of the number of digits

Congenital malformations of the limbs are among the most frequent congenital anomalies found in humans, and they preferentially affect the distal part--the hand or foot. The presence of extra digits, a condition called polydactyly, is the most common limb deformity of the human hand and is the consequence of disturbances in the normal program of limb development. However, despite the extensive use of the developing limb as a classical developmental model, the cellular and genetic mechanisms that control the number and identity of the digits are not completely understood. The aim of this review is to introduce the reader to the current state of knowledge in limb development and to provide the necessary background for an understanding of how deviations from the normal developmental program may lead to polydactyly.