The Elusive “Developmental Mechanism”: What they are and how to study and test them

Few issues have garnered as much attention as that of understanding mechanisms of developmental change. Understanding mechanisms of developmental change is important because it allows researchers to go beyond studying at what age an ability emerges to understanding the processes by which those abilities develop in the first place. Despite the clear importance of mechanisms, the notion of a developmental mechanism or mechanism of developmental change remains largely undefined and there exists no clear guidance on how to study these mechanisms systematically in the developmental literature. Given these outstanding questions, this paper has two main aims. The first aim was to provide a clear definition of mechanisms of developmental change that aligns most closely with how most, if not all, developmental psychologists think about developmental mechanisms. The second goal was to provide concrete suggestions for how developmental scientists might study and test different kinds of mechanisms of developmental change based on their perceived manipulability. One of the main arguments of the paper is that there is no one-size-fits-all approach to studying and testing mechanisms of developmental change and that how developmental researchers study them depends crucially on their perceived manipulability.

Hydrocoel Morphogenesis Forming the Pentaradial Body Plan in a Sea Cucumber, Apostichopus Japonicus

Echinoderms constitute an animal phylum characterized by the pentaradial body plan. During the development from bilateral larvae to pentaradial adults, the formation of the multiple of five hydrocoel lobes, i.e., the buddings from the mesodermal coelom, is the firstly emerging pentameral character. The developmental mechanism underlying the hydrocoel-lobe formation should be revealed to understand the evolutionary process of this unique and highly derived body plan of echinoderms, although the morphogenetic mechanisms of hydrocoel lobes is largely uninvestigated. In this study, using the sea cucumber Apostichopus japonicus, in which the hydrocoel is easily observable, the developmental process of hydrocoel lobes was described in detail, focusing on the cell proliferation and rearrangement. Cell proliferation was not specifically distributed in the growing tips of the hydrocoel lobes and inhibition of the cell proliferation did not affect the lobe formation. During lobe formation, epithelium of the hydrocoel lobes were firstly stratified and then transformed into single-layered, suggesting that radial cell intercalation contributes to hydrocoel-lobe formation.

Biliary Atresia: Clinical Phenotypes and Aetiological Heterogeneity

Biliary atresia (BA) is an obliterative condition of the biliary tract that presents with persistent jaundice and pale stools typically in the first few weeks of life. While this phenotypic signature may be broadly similar by the time of presentation, it is likely that this is only the final common pathway with a number of possible preceding causative factors and disparate pathogenic mechanisms—i.e., aetiological heterogeneity. Certainly, there are distinguishable variants which suggest a higher degree of aetiological homogeneity such as the syndromic variants of biliary atresia splenic malformation or cat-eye syndrome, which implicate an early developmental mechanism. In others, the presence of synchronous viral infection also make this plausible as an aetiological agent though it is likely that disease onset is from the perinatal period. In the majority of cases, currently termed isolated BA, there are still too few clues as to aetiology or indeed pathogenesis.

Forebrain Architecture and Development in Cyclostomes, with Reference to the Early Morphology and Evolution of the Vertebrate Head

The vertebrate head and brain are characterized by highly complex morphological patterns. The forebrain, the most anterior division of the brain, is subdivided into the diencephalon, hypothalamus, and telencephalon from the neuromeric subdivision into prosomeres. Importantly, the telencephalon contains the cerebral cortex, which plays a key role in higher order cognitive functions in humans. To elucidate the evolution of the forebrain regionalization, comparative analyses of the brain development between extant jawed and jawless vertebrates are crucial. Cyclostomes – lampreys and hagfishes – are the only extant jawless vertebrates, and diverged from jawed vertebrates (gnathostomes) over 500 million years ago. Previous developmental studies on the cyclostome brain were conducted mainly in lampreys because hagfish embryos were rarely available. Although still scarce, the recent availability of hagfish embryos has propelled comparative studies of brain development and gene expression. By integrating findings with those of cyclostomes and fossil jawless vertebrates, we can depict the morphology, developmental mechanism, and even the evolutionary path of the brain of the last common ancestor of vertebrates. In this review, we summarize the development of the forebrain in cyclostomes and suggest what evolutionary changes each cyclostome lineage underwent during brain evolution. In addition, together with recent advances in the head morphology in fossil vertebrates revealed by CT scanning technology, we discuss how the evolution of craniofacial morphology and the changes of the developmental mechanism of the forebrain towards crown gnathostomes are causally related.

Pitx controls amphioxus asymmetric morphogenesis by promoting left-side development and repressing right-side formation

Background Left-right (LR) asymmetry is an essential feature of bilateral animals. Studies in vertebrates show that LR asymmetry formation comprises three major steps: symmetry breaking, asymmetric gene expression, and LR morphogenesis. Although much progress has been made in the first two events, mechanisms underlying asymmetric morphogenesis remain largely unknown due to the complex developmental processes deployed by vertebrate organs. Results We here addressed this question by studying Pitx gene function in the basal chordate amphioxus whose asymmetric organogenesis, unlike that in vertebrates, occurs essentially in situ and does not rely on cell migration. Pitx null mutation in amphioxus causes loss of all left-sided organs and incomplete ectopic formation of all right-sided organs on the left side, whereas Pitx partial loss-of-function leads to milder phenotypes with only some LR organs lost or ectopically formed. At the N1 to N3 stages, Pitx expression is gradually expanded from the dorsal anterior domain to surrounding regions. This leads to activation of genes like Lhx3 and/or Prop1 and Pit, which are essential for left-side organs, and downregulation of genes like Hex and/or Nkx2.1 and FoxE4, which are required for right-side organs to form ectopically on the left side. In Pitx mutants, the left-side expressed genes are not activated, while the right-side genes fail to decrease expression on the left side. In contrast, in embryos overexpressing Pitx genes, the left-side genes are induced ectopically on the right side, and the right-side genes are inhibited. Several Pitx binding sites are identified in the upstream sequences of the left-side and right-side genes which are essential for activation of the former and repression of the latter by Pitx. Conclusions Our results demonstrate that (1) Pitx is a major (although not the only) determinant of asymmetric morphogenesis in amphioxus, (2) the development of different LR organs have distinct requirements for Pitx activity, and (3) Pitx controls amphioxus LR morphogenesis probably through inducing left-side organs and inhibiting right-side organs directly. These findings show much more dependence of LR organogenesis on Pitx in amphioxus than in vertebrates. They also provide insight into the molecular developmental mechanism of some vertebrate LR organs like the lungs and atria, since they show a right-isomerism phenotype in Pitx2 knockout mice like right-sided organs in Pitx mutant amphioxus. Our results also explain why some organs like the adenohypophysis are asymmetrically located in amphioxus but symmetrically positioned in vertebrates.

The Temporal Mechanisms Guiding Interneuron Differentiation in the Spinal Cord

Neurogenesis timing is an essential developmental mechanism for neuronal diversity and organization throughout the central nervous system. In the mouse spinal cord, growing evidence is beginning to reveal that neurogenesis timing acts in tandem with spatial molecular controls to diversify molecularly and functionally distinct post-mitotic interneuron subpopulations. Particularly, in some cases, this temporal ordering of interneuron differentiation has been shown to instruct specific sensorimotor circuit wirings. In zebrafish, in vivo preparations have revealed that sequential neurogenesis waves of interneurons and motor neurons form speed-dependent locomotor circuits throughout the spinal cord and brainstem. In the present review, we discuss temporal principals of interneuron diversity taken from both mouse and zebrafish systems highlighting how each can lend illuminating insights to the other. Moving forward, it is important to combine the collective knowledge from different systems to eventually understand how temporally regulated subpopulation function differentially across speed- and/or state-dependent sensorimotor movement tasks.

Why heel spurs are traction spurs after all

It is unclear whether plantar and posterior heel spurs are truly pathological findings and whether they are stimulated by traction or compression forces. Previous histological investigations focused on either one of the two spur locations, thereby potentially overlooking common features that refer to a uniform developmental mechanism. In this study, 19 feet from 16 cadavers were X-ray scanned to preselect calcanei with either plantar or posterior spurs. Subsequently, seven plantar and posterior spurs were histologically assessed. Five spur-free Achilles tendon and three plantar fascia entheses served as controls. Plantar spurs were located either intra- or supra-fascial whereas all Achilles spurs were intra-fascial. Both spur types consistently presented a trabecular architecture without a particular pattern, fibrocartilage at the tendinous entheses and the orientation of the spur tips was in line with the course of the attached soft tissues. Spurs of both entities revealed tapered areas close to their bases with bulky tips. Achilles and plantar heel spurs seem to be non-pathological calcaneal exostoses, which are likely results of traction forces. Both spur types revealed commonalities such as their trabecular architecture or the tip direction in relation to the attached soft tissues. Morphologically, heel spurs seem poorly adapted to compressive loads.

Reproductive Soldier Development Is Controlled by Direct Physical Interactions with Reproductive and Soldier Termites

In eusocial insects (e.g., ants, bees, and termites), the roles of different castes are assigned to different individuals. These castes possess unique phenotypes that are specialized for specific tasks. The acquisition of sterile individuals with specific roles is considered a requirement for social evolution. In termites, the soldier is a sterile caste. In primitive taxa (family Archotermopsidae and Stolotermitidae), however, secondary reproductives (neotenic reproductives) with their mandibles developed into weapons (so-called reproductive soldiers, also termed as soldier-headed reproductives or soldier neotenics) have been reported. To understand the developmental mechanism of this unique caste, it is necessary to understand the environmental cues and developmental processes of reproductive soldiers under natural conditions. Here, we established efficient conditions to induce reproductive soldiers in Zootermopsis nevadensis. Male reproductive soldiers frequently developed after the removal of both the king and soldiers from an incipient colony. Similarly, high differentiation rates of male reproductive soldiers were observed after king-and-soldier separation treatment using wire mesh. However, no male reproductive soldiers were produced without direct interaction with the queen. These results suggest that male reproductive soldier development is repressed by direct physical interactions with both the king and soldiers and facilitated by direct physical interaction with the queen.

Mechanism and Theories for Delayed Onset of Muscle Soreness in Athletes

The sensation of tenderness and tightness over the muscle, post eccentric exercise is called Delayed Onset of Muscle Soreness (DOMS). It is not an acute pain. Post exercise the soreness will develop within 24-72 hours of duration, slowly the soreness will reduce by 5-7 days post exercise. Initially Theodre Hough, mentioned soreness will develop when an untrained muscle does a contraction opposite to the strong spring. The aim of this review article is to find out the various mechanisms and theories for Delayed Onset of Muscle Soreness development. A direct search of journals was conducted to identify the potential articles. Online search engines such as PubMed, Google Scholar, MEDLINE, and Physiotherapy Evidence-based Database (PEDro) were searched. Based on the available research studies, Delayed onset of muscle soreness developmental mechanism was understood. Literature search helped to understand the various theories on development of DOMS and physiology behind the soreness. Still more articles and research must emerge to provide the clear evidence on theories on Delayed Onset of Muscle Soreness.

Genetical control of 2D pattern and depth of the primordial furrow that prefigures 3D shape of the rhinoceros beetle horn

The head horn of the Asian rhinoceros beetle develops as an extensively folded primordium before unfurling into its final 3D shape at the pupal molt. The information of the final 3D structure of the beetle horn is prefigured in the folding pattern of the developing primordium. However, the developmental mechanism underlying epithelial folding of the primordium is unknown. In this study, we addressed this gap in our understanding of the developmental patterning of the 3D horn shape of beetles by focusing on the formation of furrows at the surface of the primordium that become the bifurcated 3D shape of the horn. By gene knockdown analysis via RNAi, we found that knockdown of the gene Notch disturbed overall horn primordial furrow depth without affecting the 2D furrow pattern. In contrast, knockdown of CyclinE altered 2D horn primordial furrow pattern without affecting furrow depth. Our results show how the depth and 2D pattern of primordial surface furrows are regulated at least partially independently during beetle horn development, and how both can alter the final 3D shape of the horn.