A sense of place, many times over - pattern formation and evolution of repetitive morphological structures

Fifty years ago, Lewis Wolpert introduced the concept of "positional information" to explain how patterns form in a multicellular embryonic field. Using morphogen gradients, whose continuous distributions of positional values are discretized via thresholds into distinct cellular states, he provided, at the theoretical level, an elegant solution to the "French Flag problem." In the intervening years, many experimental studies have lent support to Wolpert's ideas. However, the embryonic patterning of highly repetitive morphological structures, as often occurring in nature, can reveal limitations in the strict implementation of his initial theory, given the number of distinct threshold values that would have to be specified. Here, we review how positional information is complemented to circumvent these inadequacies, to accommodate tissue growth and pattern periodicity. In particular, we focus on functional anatomical assemblies composed of such structures, like the vertebrate spine or tetrapod digits, where the resulting segmented architecture is intrinsically linked to periodic pattern formation and unidirectional growth. These systems integrate positional information and growth with additional patterning cues that, we suggest, increase robustness and evolvability. We discuss different experimental and theoretical models to study such patterning systems, and how the underlying processes are modulated over evolutionary timescales to enable morphological diversification

Evolution of High Trophic Diversity Based on Limited Functional Disparity in the Feeding Apparatus of Marine Angelfishes (f. Pomacanthidae)

The use of biting to obtain food items attached to the substratum is an ecologically widespread and important mode of feeding among aquatic vertebrates, which rarely has been studied. We did the first evolutionary analyses of morphology and motion kinematics of the feeding apparatus in Indo-Pacific members of an iconic family of biters, the marine angelfishes (f. Pomacanthidae). We found clear interspecific differences in gut morphology that clearly reflected a wide range of trophic niches. In contrast, feeding apparatus morphology appeared to be conserved. A few unusual structural innovations enabled angelfishes to protrude their jaws, close them in the protruded state, and tear food items from the substratum at a high velocity. Only one clade, the speciose pygmy angelfishes, showed functional departure from the generalized and clade-defining grab-and-tearing feeding pattern. By comparing the feeding kinematics of angelfishes with wrasses and parrotfishes (f. Labridae) we showed that grab-and-tearing is based on low kinematics disparity. Regardless of its restricted disparity, the grab-and-tearing feeding apparatus has enabled angelfishes to negotiate ecological thresholds: Given their widely different body sizes, angelfishes can access many structurally complex benthic surfaces that other biters likely are unable to exploit. From these surfaces, angelfishes can dislodge sturdy food items from their tough attachments. Angelfishes thus provide an intriguing example of a successful group that appears to have evolved considerable trophic diversity based on an unusual yet conserved feeding apparatus configuration that is characterized by limited functional disparity

Hedgehog/notch-induced premature gliogenesis represents a new disease mechanism for Hirschsprung disease in mice and humans

Hirschsprung (HSCR) disease is a complex genetic disorder attributed to a failure of the enteric neural crest cells (ENCCs) to form ganglia in the hindgut. Hedgehog and Notch are implicated in mediating proliferation and differentiation of ENCCs. Nevertheless, how these signaling molecules may interact to mediate gut colonization by ENCCs and contribute to a primary etiology for HSCR are not known. Here, we report our pathway- based epistasis analysis of data generated by a genome-wide association study on HSCR disease, which indicates that specific genotype constellations of Patched (PTCH1) (which encodes a receptor for Hedgehog) and delta-like 3 (DLL3) (which encodes a receptor for Notch) SNPs confer higher risk to HSCR. Importantly, deletion of Ptch1 in mouse ENCCs induced robust Dll1 expression and activation of the Notch pathway, leading to premature gliogenesis and reduction of ENCC progenitors in mutant bowels. Dll1 integrated Hedgehog and Notch pathways to coordinate neuronal and glial cell differentiation during enteric nervous system development. In addition, Hedgehog-mediated gliogenesis was found to be highly conserved, such that Hedgehog was consistently able to promote gliogenesis of human neural crest-related precursors. Collectively, we defined PTCH1 and DLL3 as HSCR susceptibility genes and suggest that Hedgehog/Notch-induced premature gliogenesis may represent a new disease mechanism for HSCR.published_or_final_versio

Bipartite life cycle of coral reef fishes promotes increasing shape disparity of the head skeleton during ontogeny: an example from damselfishes (Pomacentridae)

Background: Quantitative studies of the variation of disparity during ontogeny exhibited by the radiation of coral reef fishes are lacking. Such studies dealing with the variation of disparity, i.e. the diversity of organic form, over ontogeny could be a first step in detecting evolutionary mechanisms in these fishes. The damselfishes (Pomacentridae) have a bipartite life-cycle, as do the majority of demersal coral reef fishes. During their pelagic dispersion phase, all larvae feed on planktonic prey. On the other hand, juveniles and adults associated with the coral reef environment show a higher diversity of diets. Using geometric morphometrics, we study the ontogenetic dynamic of shape disparity of different head skeletal units (neurocranium, suspensorium and opercle, mandible and premaxilla) in this fish family. We expected that larvae of different species might be relatively similar in shapes. Alternatively, specialization may become notable even in the juvenile and adult phase. Results: The disparity levels increase significantly throughout ontogeny for each skeletal unit. At settlement, all larval shapes are already species-specific. Damselfishes show high levels of ontogenetic allometry during their postsettlement growth. The divergence of allometric patterns largely explains the changes in patterns and levels of shape disparity over ontogeny. The rate of shape change and the length of ontogenetic trajectories seem to be less variable among species. We also show that the high levels of shape disparity at the adult stage are correlated to a higher level of ecological and functional diversity in this stage. Conclusion: Diversification throughout ontogeny of damselfishes results from the interaction among several developmental novelties enhancing disparity. The bipartite life-cycle of damselfishes exemplifies a case where the variation of environmental factors, i.e. the transition from the more homogeneous oceanic environment to the coral reef offering a wide range of feeding habits, promotes increasing shape disparity of the head skeleton over the ontogeny of fishes

The Cyprinodon variegatus genome reveals gene expression changes underlying differences in skull morphology among closely related species

Genes in durophage intersection set at 15 dpf. This is a comma separated table of the genes in the 15 dpf durophage intersection set. Given are edgeR results for each pairwise comparison. Columns indicating whether a gene is included in the intersection set at a threshold of 1.5 or 2 fold are provided. (CSV 13 kb

The effects of knee joint angle on neuromuscular activity during electrostimulation in healthy older adults

Introduction Electrostimulation devices stimulate the common peroneal nerve, producing a calf muscle-pump action to promote venous circulation. Whether knee joint angle influences calf neuromuscular activity remains unclear. Our aim was to determine the effects of knee joint angle on lower limb neuromuscular activity during electrostimulation. Methods Fifteen healthy, older adults underwent 60 min of electrostimulation, with the knee joint at three different angles (0°, 45° or 90° flexion; random order; 20 min each). Outcome variables included electromyography of the peroneus longus, tibialis anterior and gastrocnemius medialis and lateralis and discomfort. Results Knee angle did not influence tibialis anterior and peroneus longus neuromuscular activity during electrostimulation. Neuromuscular activity was greater in the gastrocnemius medialis (p = 0.002) and lateralis (p = 0.002) at 90°, than 0° knee angle. Electrostimulation intensity was positively related to neuromuscular activity for each muscle, with a knee angle effect for the gastrocnemius medialis (p = 0.05). Conclusion Results suggest that during electrostimulation, knee joint angle influenced gastrocnemii neuromuscular activity; increased gastrocnemius medialis activity across all intensities (at 90°), when compared to 0° and 45° flexion; and did not influence peroneus longus and tibialis anterior activity. Greater electrostimulation-evoked gastrocnemii activity has implications for producing a more forceful calf muscle-pump action, potentially further improving venous flow

Trackways Produced by Lungfish During Terrestrial Locomotion

Some primarily aquatic vertebrates make brief forays onto land, creating traces as they do. A lack of studies on aquatic trackmakers raises the possibility that such traces may be ignored or misidentified in the fossil record. Several terrestrial Actinopterygian and Sarcopterygian species have previously been proposed as possible models for ancestral tetrapod locomotion, despite extant fishes being quite distinct from Devonian fishes, both morphologically and phylogenetically. Although locomotion has been well-studied in some of these taxa, trackway production has not. We recorded terrestrial locomotion of a 35 cm African lungfish (Protopterus annectens; Dipnoi: Sarcopterygii) on compliant sediment. Terrestrial movement in the lungfish is accomplished by planting the head and then pivoting the trunk. Impressions are formed where the head impacts the substrate, while the body and fins produce few traces. The head leaves a series of alternating left-right impressions, where each impact can appear as two separate semi-circular impressions created by the upper and lower jaws, bearing some similarity to fossil traces interpreted as footprints. Further studies of trackways of extant terrestrial fishes are necessary to understand the behavioural repertoire that may be represented in the fossil track record

Injectable Materials for the Treatment of Myocardial Infarction and Heart Failure: The Promise of Decellularized Matrices

Cardiovascular disease continues to be the leading cause of death, suggesting that new therapies are needed to treat the progression of heart failure post-myocardial infarction. As cardiac tissue has a limited ability to regenerate itself, experimental biomaterial therapies have focused on the replacement of necrotic cardiomyocytes and repair of the damaged extracellular matrix. While acellular and cellular cardiac patches are applied surgically to the epicardial surface of the heart, injectable materials offer the prospective advantage of minimally invasive delivery directly into the myocardium to either replace the damaged extracellular matrix or to act as a scaffold for cell delivery. Cardiac-specific decellularized matrices offer the further advantage of being biomimetic of the native biochemical and structural matrix composition, as well as the potential to be autologous therapies. This review will focus on the requirements of an ideal scaffold for catheter-based delivery as well as highlight the promise of decellularized matrices as injectable materials for cardiac repair