Developmental Genetic Mechanisms Research Articles

The role of cytokines and their genetic polymorphism in the development of hypoxic-ischemic encephalopathy among full-term newborn children

The problem of ischemic brain damage among newborns is still relevant in the modern world. The frequency of occurrence of this pathology among full-term newborns remains at a fairly high level, both in Russia and abroad. Moreover, it has a high mortality rate and the percentage of early childhood disability is 60-70%, participating in the development of such diseases as minimal brain dysfunction, infantile cerebral palsy, epilepsy. According to the World Health Organization, about 20% of children suffer from neuropsychic disorders, whose causes in 65-80% of cases are perinatal brain lesions of hypoxic origin. The article deals with modern concepts of molecular genetic mechanisms of development of hypoxic-ischemic encephalopathy among newborns, as well as issues of classification and conditions under which this pathology develops. The author studied the latest domestic and foreign literature data on the properties and role of pro and anti-inflammatory cytokines, such as IL-1, IL-4, IL-6, IL-8, IL-10, IL-13, TNF-α, which are, according to modern concepts, one of the main links in the pathogenesis of ischemic brain injury. Also, special attention is paid to their genetic polymorphism, since qualitatively or quantitatively the genetically altered molecules of cytokines affect the immune response. Investigation of the level of cytokines and their genetic polymorphism before the onset of clinical symptoms will allow prediction the onset of the disease and preventing the adverse effects of the damage of the central nervous system.

Developmental timing differences underlie armor loss across threespine stickleback populations.

Comparing ontogenetic patterns within a well-described evolutionary context aids in inferring mechanisms of change, including heterochronies or deletion of developmental pathways. Because selection acts on phenotypes throughout ontogeny, any within-taxon developmental variation has implications for evolvability. We compare ontogenetic order and timing of locomotion and defensive traits in three populations of threespine stickleback that have evolutionarily divergent adult forms. This analysis adds to the growing understanding of developmental genetic mechanisms of adaptive change in this evolutionary model species by delineating when chondrogenesis and osteogenesis in two derived populations begin to deviate from the developmental pattern in their immediate ancestors. We found that differences in adult defensive morphologies arise through abolished or delayed initiation of these traits rather than via an overall heterochronic shift, that intra-population ontogenetic variation is increased for some derived traits, and that altered armor developmental timing differentiates the derived populations from each other despite parallels in adult lateral plate armor phenotypes. We found that changes in ossified elements of the pelvic armor are linked to delayed and incomplete development of an early-forming pelvic cartilage, and that this disruption likely presages the variable pelvic vestiges documented in many derived populations.

Implications of Vertebrate Craniodental Evo-Devo for Human Oral Health.

Highly processed diets eaten by postindustrial modern human populations coincide with higher frequencies of third molar impaction, malocclusion, and temporomandibular joint disorders that affect millions of people worldwide each year. Current treatments address symptoms, not causes, because the multifactorial etiologies of these three concerns mask which factors incline certain people to malocclusion, impaction, and/or joint issues. Deep scientific curiosity about the origins of jaws and dentitions continues to yield rich insights about the developmental genetic mechanisms that underpin healthy craniodental morphogenesis and integration. Mounting evidence from evolution and development (Evo-Devo) studies suggests that function is another mechanism important to healthy craniodental integration and fit. Starting as early as weaning, softer diets and thus lower bite forces appear to relax or disrupt integration of oral tissues, alter development and growth, and catalyze impaction, malocclusion, and jaw joint disorders. How developing oral tissues respond to bite forces remains poorly understood, but biomechanical feedback seems to alter balances of local bone resorption and deposition at the tooth-bone interface as well as affect tempos and amounts of facial outgrowth. Also, behavioral changes in jaw function and parafunction contribute to degeneration and pain in joint articular cartilages and masticatory muscles. The developmental genetic contribution to craniodental misfits and disorders is undeniable but still unclear; however, at present, human diet and jaw function remain important and much more actionable clinical targets. New Evo-Devo studies are needed to explain how function interfaces with craniodental phenotypic plasticity, variation, and evolvability to yield a spectrum of healthy and mismatched dentitions and jaws.

Phasmarhabditis hermaphrodita – a new model to study the genetic evolution of parasitism

The evolutionary genetic mechanisms that are responsible for the transition of free-living nematodes to parasites are unknown and current nematode models used to study this have limitations. The gastropod parasitePhasmarhabditis hermaphroditacould be used as a new model to dissect the molecular mechanisms involved in the evolution of parasitism.Phasmarhabditis hermaphroditais a facultative parasite of slugs and snails that, likeCaenorhabditis elegansandPristionchus pacificus, can also be maintained easily under laboratory conditions.Phasmarhabditis hermaphroditaandPhasmarhabditisspecies are easy to isolate from the wild and have been found around the world. The phylogenetic position ofPhasmarhabditisis ideal for genomic comparison with other clade 9 species such asC. elegansandP. pacificus, as well as mammalian and insect parasites. These attributes could makeP. hermaphroditaan excellent choice of model to study the evolutionary emergence of parasitism.

Conservation, Innovation, and Bias: Embryonic Segment Boundaries Position Posterior, but Not Anterior, Head Horns in Adult Beetles

The integration of form and function of novel traits is a fundamental process during the developmental evolution of complex organisms, yet how novel traits and trait functions integrate into preexisting contexts remains poorly understood. Here, we explore the mechanisms by which the adult insect head has been able to integrate novel traits and features during its ontogeny, focusing on the cephalic horns of Onthophagus beetles. Specifically, using a microablation approach we investigate how different regions of the dorsal head of adult horned beetles relate to their larval and embryonic counterparts and test whether deeply conserved regional boundaries that establish the embryonic head might also facilitate or bias the positioning of cephalic horns along the dorsal adult head. We find that paired posterior horns-the most widespread horn type within the genus-are positioned along a border homologous to the embryonic clypeolabral (CL)-ocular boundary, and that this placement constitutes the ancestral form of horn positioning. In contrast, we observed that the phylogenetically much rarer anterior horns are positioned by larval head regions contained firmly within the CL segment and away from any major preexisting larval head landmarks or boundaries. Lastly, we describe the unexpected finding that ablations at medial head regions can result in ectopic outgrowths bearing terminal structures resembling the more anterior clypeal ridge. We discuss our results in the light of the developmental genetic mechanisms of head formation in holometabolous insects and the role of co-option in innovation and bias in developmental evolution.

Introduction to 'Homology and convergence in nervous system evolution'.

The origin of brains and central nervous systems (CNSs) is thought to have occurred before the Palaeozoic era 540 Ma. Yet in the absence of tangible evidence, there has been continued debate whether today's brains and nervous systems derive from one ancestral origin or whether similarities among them are due to convergent evolution. With the advent of molecular developmental genetics and genomics, it has become clear that homology is a concept that applies not only to morphologies, but also to genes, developmental processes, as well as to behaviours. Comparative studies in phyla ranging from annelids and arthropods to mammals are providing evidence that corresponding developmental genetic mechanisms act not only in dorso-ventral and anterior-posterior axis specification but also in segmentation, neurogenesis, axogenesis and eye/photoreceptor cell formation that appear to be conserved throughout the animal kingdom. These data are supported by recent studies which identified Mid-Cambrian fossils with preserved soft body parts that present segmental arrangements in brains typical of modern arthropods, and similarly organized brain centres and circuits across phyla that may reflect genealogical correspondence and control similar behavioural manifestations. Moreover, congruence between genetic and geological fossil records support the notion that by the 'Cambrian explosion' arthropods and chordates shared similarities in brain and nervous system organization. However, these similarities are strikingly absent in several sister- and outgroups of arthropods and chordates which raises several questions, foremost among them: what kind of natural laws and mechanisms underlie the convergent evolution of such similarities? And, vice versa: what are the selection pressures and genetic mechanisms underlying the possible loss or reduction of brains and CNSs in multiple lineages during the course of evolution? These questions were addressed at a Royal Society meeting to discuss homology and convergence in nervous system evolution. By integrating knowledge ranging from evolutionary theory and palaeontology to comparative developmental genetics and phylogenomics, the meeting covered disparities in nervous system origins as well as correspondences of neural circuit organization and behaviours, all of which allow evidence-based debates for and against the proposition that the nervous systems and brains of animals might derive from a common ancestor.

Genetic mechanisms control the linear scaling between related cortical primary and higher order sensory areas.

In mammals, the neocortical layout consists of few modality-specific primary sensory areas and a multitude of higher order ones. Abnormal layout of cortical areas may disrupt sensory function and behavior. Developmental genetic mechanisms specify primary areas, but mechanisms influencing higher order area properties are unknown. By exploiting gain-of and loss-of function mouse models of the transcription factor Emx2, we have generated bi-directional changes in primary visual cortex size in vivo and have used it as a model to show a novel and prominent function for genetic mechanisms regulating primary visual area size and also proportionally dictating the sizes of surrounding higher order visual areas. This finding redefines the role for intrinsic genetic mechanisms to concomitantly specify and scale primary and related higher order sensory areas in a linear fashion.

Multiple Phylogenetically Distinct Events Shaped the Evolution of Limb Skeletal Morphologies Associated with Bipedalism in the Jerboas

Recent rapid advances in experimental biology have expanded the opportunity for interdisciplinary investigations of the evolution of form and function in non-traditional model species. However, historical divisions of philosophy and methodology between evolutionary/organismal biologists and developmental geneticists often preclude an effective merging of disciplines. In an effort to overcome these divisions, we take advantage of the extraordinary morphological diversity of the rodent superfamily Dipodoidea, including the bipedal jerboas, to experimentally study the developmental mechanisms and biomechanical performance of a remarkably divergent limb structure. Here, we place multiple limb character states in a locomotor and phylogenetic context. Whereas obligate bipedalism arose just once in the ancestor of extant jerboas, we find that digit loss, metatarsal fusion, between-limb proportions, and within-hindlimb proportions all evolved independently of one another. Digit loss occurred three times through at least two distinct developmental mechanisms, and elongation of the hindlimb relative to the forelimb is not simply due to growth mechanisms that change proportions within the hindlimb. Furthermore, we find strong evidence for punctuated evolution of allometric scaling of hindlimb elements during the radiation of Dipodoidea. Our work demonstrates the value of leveraging the evolutionary history of a clade to establish criteria for identifying the developmental genetic mechanisms of morphological diversification.

Predator strike shapes antipredator phenotype through new genetic interactions in water striders.

How novel genetic interactions evolve, under what selective pressures, and how they shape adaptive traits is often unknown. Here we uncover behavioural and developmental genetic mechanisms that enable water striders to survive attacks by bottom-striking predators. Long midlegs, critical for antipredator strategy, are shaped through a lineage-specific interaction between the Hox protein Ultrabithorax (Ubx) and a new target gene called gilt. The differences in leg morphologies are established through modulation of gilt differential expression between mid and hindlegs under Ubx control. Furthermore, short-legged water striders, generated through gilt RNAi knockdown, exhibit reduced performance in predation tests. Therefore, the evolution of the new Ubx–gilt interaction contributes to shaping the legs that enable water striders to dodge predator strikes. These data show how divergent selection, associated with novel prey–predator interactions, can favour the evolution of new genetic interactions and drive adaptive evolution.

A test of genetic models for the evolutionary maintenance of same-sex sexual behaviour.

The evolutionary maintenance of same-sex sexual behaviour (SSB) has received increasing attention because it is perceived to be an evolutionary paradox. The genetic basis of SSB is almost wholly unknown in non-human animals, though this is key to understanding its persistence. Recent theoretical work has yielded broadly applicable predictions centred on two genetic models for SSB: overdominance and sexual antagonism. Using Drosophila melanogaster, we assayed natural genetic variation for male SSB and empirically tested predictions about the mode of inheritance and fitness consequences of alleles influencing its expression. We screened 50 inbred lines derived from a wild population for male-male courtship and copulation behaviour, and examined crosses between the lines for evidence of overdominance and antagonistic fecundity selection. Consistent variation among lines revealed heritable genetic variation for SSB, but the nature of the genetic variation was complex. Phenotypic and fitness variation was consistent with expectations under overdominance, although predictions of the sexual antagonism model were also supported. We found an unexpected and strong paternal effect on the expression of SSB, suggesting possible Y-linkage of the trait. Our results inform evolutionary genetic mechanisms that might maintain low but persistently observed levels of male SSB in D. melanogaster, but highlight a need for broader taxonomic representation in studies of its evolutionary causes.

Developmental genetic mechanisms of C4 syndrome based on transcriptome analysis of C3 cotyledons and C4 assimilating shoots in Haloxylon ammodendron.

It is believed that transferring the C4 engine into C3 crops will greatly increase the yields of major C3 crops. Many efforts have been made since the 1960s, but relatively little success has been achieved because C4plant traits, referred to collectively as C4 syndrome, are very complex, and little is known about the genetic mechanisms involved. Unfortunately, there exists no ideal genetic model system to study C4 syndrome. It was previously reported that the Haloxylon species have different photosynthetic pathways in different photosynthetic organs, cotyledons and assimilating shoots. Here, we took advantage of the developmental switch from the C3 to the C4 pathway to study the genetic mechanisms behind this natural transition. We compared the transcriptomes of cotyledons and assimilating shoots using mRNA-Seq to gain insight into the molecular and cellular events associated with C4 syndrome. A total of 2959 differentially expressed genes [FDR≤0.001 and abs (|log2(Fold change)|≥1)] were identified, revealing that the transcriptomes of cotyledons and assimilating shoots are considerably different. We further identified a set of putative regulators of C4 syndrome. This study expands our understanding of the development of C4 syndrome and provides a new model system for future studies on the C3-to- C4 switch mechanism.

Normally grown and developed intermuscular bone-deficient mutant in grass carp, <italic>Ctenopharyngodon idellus</italic>

An intermuscular bone-deficient grass carp, Ctenopharyngodon idellus , mutant has been identified in an artificial gynogenetic group, in which traits encoded by recessive mutant genes can be detected because of the genomic homozygosis. Both the axial and appendicular skeletons in the mutant are developed as in the gynogenetic wild-type individuals. No growth or morphological abnormalities have been observed in the mutant. These results indicate that: (1) it is unlikely that intermuscular bone is essential for body support and normal movement of grass carp; (2) the developmental genetic regulatory mechanism of intermuscular bone differs from that of the axial and appendicular skeleton; and (3) the intermuscular bone-deficient grass carp strain can be bred using advanced biological techniques. Statistical analysis revealed that the ratio of mutant grass carp with no intermuscular bone is very low in gynogenetic grass carp groups, suggesting that many genes are involved in the development of intermuscular bones and the regulatory network is quite complex. This mutant provides unique experimental material for the identification of genes involved in intermuscular bone development.

Nanosilver-based antibacterial drugs and devices: Mechanisms, methodological drawbacks, and guidelines

Despite the current advancement in drug discovery and pharmaceutical biotechnology, infection diseases induced by bacteria continue to be one of the greatest health problems worldwide, afflicting millions of people annually. Almost all microorganisms have, in fact, an intrinsic outstanding ability to flout many therapeutic interventions, thanks to their fast and easy-to-occur evolutionary genetic mechanisms. At the same time, big pharmaceutical companies are losing interest in new antibiotics development, shifting their capital investments in much more profitable research and development fields. New smart solutions are, thus, required to overcome such concerns, and should combine the feasibility of industrial production processes with cheapness and effectiveness. In this framework, nanotechnology-based solutions, and in particular silver nanoparticles (AgNPs), have recently emerged as promising candidates in the market as new antibacterial agents. AgNPs display, in fact, enhanced broad-range antibacterial/antiviral properties, and their synthesis procedures are quite cost effective. However, despite their increasing impact on the market, many relevant issues are still open. These include the molecular mechanisms governing the AgNPs-bacteria interactions, the physico-chemical parameters underlying their toxicity to prokaryotes, the lack of standardized methods and materials, and the uncertainty in the definition of general strategies to develop smart antibacterial drugs and devices based on nanosilver. In this review, we analyze the experimental data on the bactericidal effects of AgNPs, discussing the complex scenario and presenting the potential drawbacks and limitations in the techniques and methods employed. Moreover, after analyzing in depth the main mechanisms involved, we provide some general strategies/procedures to perform antibacterial tests of AgNPs, and propose some general guidelines for the design of antibacterial nanosystems and devices based on silver/nanosilver.

Opening a can of centipedes: new insights into mechanisms of body segmentation

The search for a common developmental genetic mechanism of body segmentation appears to become more difficult, and more interesting, as new segmented organisms are added to the roster. Recent work in this journal by Brena and Akam on segmentation of the geophilomorph centipede Strigamia maritima, an arthropod distantly related to the standard insect models, contains developmental and evolutionary surprises that highlight the importance of a wider sampling of phyla.See research article: http://www.biomedcentral.com/1741-7007/11/112

Evolution of the Eye Transcriptome under Constant Darkness in Sinocyclocheilus Cavefish

In adaptating to perpetual darkness, cave species gradually lose eyes and body pigmentation and evolve alternatives for exploring their environments. Although troglodyte features evolved independently many times in cavefish, we do not yet know whether independent evolution of these characters involves common genetic mechanisms. Surface-dwelling and many cave-dwelling species make the freshwater teleost genus Sinocyclocheilus an excellent model for studying the evolution of adaptations to life in constant darkness. We compared the mature retinal histology of surface and cave species in Sinocyclocheilus and found that adult cavefish showed a reduction in the number and length of photoreceptor cells. To identify genes and genetic pathways that evolved in constant darkness, we used RNA-seq to compare eyes of surface and cave species. De novo transcriptome assemblies were developed for both species, and contigs were annotated with gene ontology. Results from cave-dwelling Sinocyclocheilus revealed reduced transcription of phototransduction and other genes important for retinal function. In contrast to the blind Mexican tetra cavefish Astyanax mexicanus, our results on morphologies and gene expression suggest that evolved retinal reduction in cave-dwelling Sinocyclocheilus occurs in a lens-independent fashion by the reduced proliferation and downregulation of transcriptional factors shown to have direct roles in retinal development and maintenance, including cone-rod homeobox (crx) and Wnt pathway members. These results show that the independent evolution of retinal degeneration in cavefish can occur by different developmental genetic mechanisms.

Evidence that an evolutionary transition from dehiscent to indehiscent fruits in Lepidium (Brassicaceae) was caused by a change in the control of valve margin identity genes

In the Brassicaceae, indehiscent fruits evolved from dehiscent fruits several times independently. Here we use closely related wild species of the genus Lepidium as a model system to analyse the underlying developmental genetic mechanisms in a candidate gene approach. ALCATRAZ (ALC), INDEHISCENT (IND), SHATTERPROOF1 (SHP1) and SHATTERPROOF2 (SHP2) are known fruit developmental genes of Arabidopsis thaliana that are expressed in the fruit valve margin governing dehiscence zone formation. Comparative expression analysis by quantitative RT-PCR, Northern blot and in situ hybridization show that their orthologues from Lepidium campestre (dehiscent fruits) are similarly expressed at valve margins. In sharp contrast, expression of the respective orthologues is abolished in the corresponding tissue of indehiscent Lepidium appelianum fruits, indicating that changes in the genetic pathway identified in A.thaliana caused the transition from dehiscent to indehiscent fruits in the investigated species. As parallel mutations in different genes are quite unlikely, we conclude that the changes in gene expression patterns are probably caused by changes in upstream regulators of ALC, IND and SHP1/2, possible candidates from A.thaliana being FRUITFULL (FUL), REPLUMLESS (RPL) and APETALA2 (AP2). However, neither expression analyses nor functional tests in transgenic plants provided any evidence that the FUL or RPL orthologues of Lepidium were involved in evolution of fruit indehiscence in Lepidium. In contrast, stronger expression of AP2 in indehiscent compared to dehiscent fruits identifies AP2 as a candidate gene that deserves further investigation.

Understanding specialism when the jack of all trades can be the master of all

Specialism is widespread in nature, generating and maintaining diversity, but recent work has demonstrated that generalists can be equally fit as specialists in some shared environments. This no-cost generalism challenges the maxim that 'the jack of all trades is the master of none', and requires evolutionary genetic mechanisms explaining the existence of specialism and no-cost generalism, and the persistence of specialism in the face of selection for generalism. Examining three well-described mechanisms with respect to epistasis and pleiotropy indicates that sign (or antagonistic) pleiotropy without epistasis cannot explain no-cost generalism and that magnitude pleiotropy without epistasis (including directional selection and mutation accumulation) cannot explain the persistence of specialism. However, pleiotropy with epistasis can explain all. Furthermore, epistatic pleiotropy may allow past habitat use to influence future use of novel environments, thereby affecting disease emergence and populations' responses to habitat change.

Convergent evolution of a reproductive trait through distinct developmental mechanisms in Drosophila

Convergent morphologies often arise due to similar selective pressures in independent lineages. It is poorly understood whether the same or different developmental genetic mechanisms underlie such convergence. Here we show that independent evolution of a reproductive trait, ovariole number, has resulted from changes in distinct developmental mechanisms, each of which may have a different underlying genetic basis in Drosophila. Ovariole number in Drosophila is species-specific, highly variable, and largely under genetic control. Convergent changes in Drosophila ovariole number have evolved independently within and between species. We previously showed that the number of a specific ovarian cell type, terminal filament (TF) cells, determines ovariole number. Here we examine TF cell development in different Drosophila lineages that independently evolved a significantly lower ovariole number than the D. melanogaster Oregon R strain. We show that in these Drosophila lineages, reduction in ovariole number occurs primarily through variations in one of two different developmental mechanisms: (1) reduced number of somatic gonad precursors (SGP cells) specified during embryogenesis; or (2) alterations of somatic gonad cell morphogenesis and differentiation in larval life. Mutations in the D. melanogaster Insulin Receptor (InR) alter SGP cell number but not ovarian morphogenesis, while targeted loss of function of bric-à-brac 2 (bab2) affects morphogenesis without changing SGP cell number. Thus, evolution can produce similar ovariole numbers through distinct developmental mechanisms, likely controlled by different genetic mechanisms.

De novo Transcriptome Assembly and SNP Discovery in the Wing Polymorphic Salt Marsh Beetle Pogonus chalceus (Coleoptera, Carabidae)

BackgroundThe salt marsh beetle Pogonus chalceus represents a unique opportunity to understand and study the origin and evolution of dispersal polymorphisms as remarkable inter-population divergence in dispersal related traits (e.g. wing development, body size and metabolism) has been shown to persist in face of strong homogenizing gene flow. Sequencing and assembling the transcriptome of P. chalceus is a first step in developing large scale genetic information that will allow us to further study the recurrent phenotypic evolution in dispersal traits in these natural populations.Methodology/ResultsWe used the Illumina HiSeq2000 to sequence 37 Gbases of the transcriptome and performed de novo transcriptome assembly with the Trinity short read assembler. This resulted in 65,766 contigs, clustering into 39,393 unique transcripts (unigenes). A subset of 12,987 show similarity (BLAST) to known proteins in the NCBI database and 7,589 are assigned Gene Ontology (GO). Using homology searches we identified all reported genes involved in wing development, juvenile- and ecdysteroid hormone pathways in Tribolium castaneum. About half (56.7%) of the unique assembled genes are shared among three life stages (third-instar larva, pupa, and imago). We identified 38,141 single nucleotide polymorphisms (SNPs) in these unigenes. Of these SNPs, 26,823 (70.3%) were found in a predicted open reading frame (ORF) and 6,998 (18.3%) were nonsynonymous.ConclusionsThe assembled transcriptome and SNP data are essential genomic resources for further study of the developmental pathways, genetic mechanisms and metabolic consequences of adaptive divergence in dispersal power in natural populations.

Anatomical and functional correlates of human hippocampal volume asymmetry

Hemispheric asymmetry of the human hippocampus is well established, but poorly understood. We studied 110 healthy subjects with 3-Tesla MRI to explore the anatomical and functional correlates of the R>L volume asymmetry. We found that the asymmetry is limited to the anterior hippocampus (hemisphere×region interaction: F(1,109)=42.6, p<.001). Anterior hippocampal volume was correlated strongly with the volumes of all four cortical lobes. In contrast, posterior hippocampal volume was correlated strongly only with occipital lobe volume, moderately with the parietal and temporal lobe volumes and not with the frontal lobe volume. The degree of R>L anterior hippocampal volume asymmetry predicted performance on a measure of basic cognitive abilities. This provides evidence for regional specificity and functional implications of the well-known hemispheric asymmetry of hippocampal volume. We suggest that the developmental profile, genetic mechanisms and functional implications of R>L anterior hippocampal volume asymmetry in the human brain deserve further study.