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Darrell J R Evans

Publications and source records attributed to Darrell J R Evans.

14 recordsLinked to original sources
PubMed2006

Skeletal muscle translocation in vertebrates.

It is now over 30 years since Bodo Christ first demonstrated that the musculature of the limb originated from the somites and overturned the then prevailing view that limb muscle develops from a local source. Subsequently, using electron microscopy and histological procedures, Bodo Christ identified that cells of the somites undergo an epithelial to mesenchymal transition which enabled them to move from their paraxial point of origin to distal locations. These studies defined this translocation as one of the major mechanisms allowing myogenic cells to translocate around the body. The other means used to translocate muscle involves the movement of cells as a sheet. The deployment of one of these two mechanisms has been postulated to be involved in the formation of all the hypaxial musculature of the vertebrate body. In this paper we describe the formation of muscles both in the head and in the body, which use a translocatory mechanism during their development. We highlight recent data showing that muscle translocation is a far more complex process than first thought but which in itself can be used as a valuable tool to address questions regarding tissue patterning and development.

Animals↗
PubMed2006

Spatial relations between avian craniofacial neural crest and paraxial mesoderm cells.

Fate maps based on quail-chick grafting of avian cephalic neural crest precursors and paraxial mesoderm cells have identified the majority of derivatives from each population but have not unequivocally resolved the precise locations of and population dynamics at the interface between them. The relation between these two mesenchymal tissues is especially critical for the development of skeletal muscles, because crest cells play an essential role in their differentiation and subsequent spatial organization. It is not known whether myogenic mesoderm and skeletogenic neural crest cells establish permanent relations while en route to their final destinations, or later at the sites where musculoskeletal morphogenesis is completed. We applied beta-galactosidase-encoding, replication-incompetent retroviruses to paraxial mesoderm, to crest progenitors, or at the interface between mesodermal and overlying neural crest as both were en route to branchial or periocular regions in chick embryos. With respect to skeletal structures, the results identify the avian neural crest:mesoderm boundary at the junction of the supraorbital and calvarial regions of the frontal bone, lateral to the hypophyseal foramen, and rostral to laryngeal cartilages. Therefore, in the chick embryo, most of the frontal and the entire parietal bone are of mesodermal, not neural crest, origin. Within paraxial mesoderm, the progenitors of each lineage display different behaviors. Chondrogenic cells are relatively stationary and intramembranous osteogenic cells move only in transverse planes around the brain. Angioblasts migrate invasively in all directions. Extraocular muscle precursors form tightly aggregated masses that en masse cross the crest:mesoderm interface to enter periocular territories, while branchial myogenic lineages shift ventrally coincidental with the movements of corresponding neural crest cells. En route to the branchial arches, myogenic mesoderm cells do not maintain constant, nearest-neighbor relations with adjacent, overlying neural crest cells. Thus, progenitors of individual muscles do not establish stable, permanent relations with their connective tissues until both populations reach the sites of their morphogenesis within branchial arches or orbital regions.

Animals↗
PubMed2005

Provision of anatomical teaching in a new British medical school: getting the right mix.

In response to a government report, which recommended a substantial increase in the number of medical students in the United Kingdom by 2005, several new medical schools have been set up throughout the country. One such school, the Brighton and Sussex Medical School (BSMS), recently opened its doors to new students. BSMS offers a 5-year medical curriculum that uses an integrated systems-based approach to cultivate academic knowledge and clinical experience. Anatomy is one of the core elements of the program and, as such, features strongly within the modular curriculum. The challenge for the anatomy faculty has been to decide how best to integrate anatomy into the new curriculum and what teaching modalities should be used. A multidisciplinary approach has been taken using both traditional and contemporary teaching methods. Unlike most of the other new medical schools, BSMS uses cadaveric dissection as the cornerstone of its teaching, as the faculty believes that dissection still provides the most powerful technique for demonstrating anatomy as well as enhancing communication and teamwork skills. The dissection experience is handled using an understanding and professional way. However, to ensure that our students do not become detached from the process of patient-focused care, emphasis in the dissecting room environment is also placed on respect and compassion. To enhance conceptual understanding of structure and function and provide further clinical relevance, we are using imaging technology to demonstrate living anatomy. Unique to the BSMS curriculum is the teaching of the anatomy in the later years of the program. During specialist rotations, students will return to the dissecting room to study the anatomy relevant to that area. Such vertical integration ensures that core anatomical knowledge is gained at the most appropriate level relative to a student's clinical experience.

Anatomy↗
PubMed2005

A dual fate of the hindlimb muscle mass: cloacal/perineal musculature develops from leg muscle cells.

The cloaca serves as a common opening to the urinary and digestive systems. In most mammals, the cloaca is present only during embryogenesis, after which it undergoes a series of septation events leading to the formation of the anal canal and parts of the urogenital tract. During embryogenesis it is surrounded by skeletal muscle. The origin and the mechanisms regulating the development of these muscles have never been determined. Here, we show that the cloacal muscles of the chick originate from somites 30-34, which overlap the domain that gives rise to leg muscles (somites 26-33). Using molecular and cell labelling protocols, we have determined the aetiology of cloacal muscles. Surprisingly, we found that chick cloacal myoblasts first migrate into the developing leg bud and then extend out of the ventral muscle mass towards the cloacal tubercle. The development of homologous cloacal/perineal muscles was also examined in the mouse. Concordant with the results in birds, we found that perineal muscles in mammals also develop from the ventral muscle mass of the hindlimb. We provide genetic evidence that the perineal muscles are migratory, like limb muscles, by showing that they are absent in metd/d mutants. Using experimental embryological procedures (in chick) and genetic models (in chick and mouse), we show that the development of the cloacal musculature is dependent on proximal leg field formation. Thus, we have discovered a novel developmental mechanism in vertebrates whereby muscle cells first migrate from axially located somites to the pelvic limb, then extend towards the midline and only then differentiate into the single cloacal/perineal muscles.

Animals↗
PubMed2004

The surface of articular cartilage contains a progenitor cell population.

It is becoming increasingly apparent that articular cartilage growth is achieved by apposition from the articular surface. For such a mechanism to occur, a population of stem/progenitor cells must reside within the articular cartilage to provide transit amplifying progeny for growth. Here, we report on the isolation of an articular cartilage progenitor cell from the surface zone of articular cartilage using differential adhesion to fibronectin. This population of cells exhibits high affinity for fibronectin, possesses a high colony-forming efficiency and expresses the cell fate selector gene Notch 1. Inhibition of Notch signalling abolishes colony forming ability whilst activated Notch rescues this inhibition. The progenitor population also exhibits phenotypic plasticity in its differentiation pathway in an embryonic chick tracking system, such that chondroprogenitors can engraft into a variety of connective tissue types including bone, tendon and perimysium. The identification of a chondrocyte subpopulation with progenitor-like characteristics will allow for advances in our understanding of both cartilage growth and maintenance as well as provide novel solutions to articular cartilage repair.

Amyloid Precursor Protein Secretases↗
PubMed2004

Changes in the proportion and number of Pax(7+ve) and MF20(+ve) myoblasts during chick myogenesis in the head and limb.

Previous studies suggested that all myoblasts are present in the head and limb prior to the commencement of primary myotube formation. As a consequence, these myoblasts must be in various developmental states during myogenesis, i.e. proliferating, differentiating or terminally differentiated. There are few in vivo studies investigating dynamic quantitative changes of subgroups of these myoblasts during myogenesis. In this report, using anti-Pax7 and anti-myosin heavy chain antibodies, we examined the quantitative change of proliferating (Pax7(+ve)) and terminally differentiated (MF20(+ve)) myoblasts during primary and secondary myogenesis in the chick head and limb. Our results show that during primary myogenesis, less than 30% of myoblasts are in the proliferating phase, but as soon as secondary myogenesis begins, over 95% of myoblasts start to proliferate. Moreover, we have found that the proportion of terminally differentiated myoblasts is maintained at a low level (less than 3%) during primary and secondary myogenesis.

Animals↗
PubMed2003

Contribution of somitic cells to the avian ribs.

The traditional view that all parts of the ribs originate from the sclerotome of the thoracic somites has recently been challenged by an alternative view suggesting that only the proximal rib derives from the sclerotome, while the distal rib arises from regions of the dermomyotome. In view of this continuing controversy and to learn more about the cell interactions during rib morphogenesis, this study aimed to reveal the precise contributions made by somitic cells to the ribs and associated tissues of the thoracic cage. A replication-deficient lacZ-encoding retrovirus was utilized to label cell populations within distinct regions of somites 19-26 in stage 13-18 chick embryos. Analysis of the subsequent contributions made by these cells revealed that the thoracic somites are the sole source of cells for the ribs. More precisely, it is the sclerotome compartment of the somites that contributes cells to both the proximal and distal elements of the ribs, confirming the traditional view of the origin of the ribs. Results also indicate that the precursor cells of the ribs and intercostal muscles are intimately associated within the somite, a relationship that may be essential for proper rib morphogenesis. Finally, the data from this study also show that the distal ribs are largely subject to resegmentation, although cell mixing may occur at the most sternal extremities.

Animals↗
PubMed2003

Spatial and temporal contribution of somitic myoblasts to avian hind limb muscles.

Skeletal muscles of the avian limb are derived from mononucleated myogenic precursor cells (myoblasts) that migrate into the somatopleural mesoderm of the developing limb bud from the ventrolateral dermomyotome of limb adjacent somites. In the present study, we utilized replication-deficient lacZ-encoding retroviruses to elucidate the source of myoblasts for all hind limb muscles in the chick and define the distinct patterns of myoblast distribution within the limb. We also examined, using the same marker, whether the time of migration from the somites into the limb dictates the spatial contribution the myoblasts make to the developing musculature, particularly in relation to the proximodistal and dorsovental axes. Finally, we used these investigations to examine whether the precursors of both primary and secondary myotubes are derived from somitic mesoderm, a presumption, which up until now, has not been demonstrated in vivo. Overall, the results of our studies demonstrate that individual somites have a selective spatial pattern of participation in the development of the avian hind limb musculature and contribute to both primary and secondary myotubes. We also show that both early and later migrating myoblasts can contribute fully to the formation of the appendicular muscles.

Animals↗
PubMed2003

Tendon morphogenesis in the developing avian limb: plasticity of fetal tendon fibroblasts.

The differentiation and patterning of tendon fibroblasts is at present a poorly understood aspect of musculoskeletal development in the vertebrate limb. Precursors of tendon fibroblasts originate in the somatic mesoderm adjacent to the early limb bud and gradually become incorporated into the limb mesenchyme as development proceeds. It is unclear whether these progenitor cells are committed to the tendon lineage at this early stage, or whether cells become committed only as they are incorporated into a developing tendon. Following a review of our current knowledge of early tendon development, we present recent results from our preliminary studies looking at tendon cell commitment. Using a lacZ encoding replication-deficient retrovirus, we have mapped regions of the early limb bud that contain presumptive tendon progenitor cells, and later used these sites for implanting labelled fetal tendon fibroblasts into developing limbs. Following implantation, we found that these cells successfully re-incorporated into developing proximal and distal tendons, but also surprisingly contributed to other tissue lineages within the limb. Our results suggest that fetal tendon fibroblasts may not be irreversibly committed to a tendon cell fate in the limb and may be somewhat plastic in their ability to integrate into other tissue lineages during development.

Animals↗
PubMed2003

Wnt signalling regulates myogenic differentiation in the developing avian wing.

The limb musculature arises by delamination of premyogenic cells from the lateral dermomyotome. Initially the cells express Pax3 but, upon entering the limb bud, they switch on the expression of MyoD and Myf5 and undergo terminal differentiation into slow or fast fibres, which have distinct contractile properties that determine how a muscle will function. In the chick, the premyogenic cells express the Wnt antagonist Sfrp2, which is downregulated as the cells differentiate, suggesting that Wnts might regulate myogenic differentiation. Here, we have investigated the role of Wnt signalling during myogenic differentiation in the developing chick wing bud by gain- and loss-of-function studies in vitro and in vivo. We show that Wnt signalling changes the number of fast and/or slow fibres. For example, in vivo, Wnt11 decreases and increases the number of slow and fast fibres, respectively, whereas overexpression of Wnt5a or a dominant-negative Wnt11 protein have the opposite effect. The latter shows that endogenous Wnt11 signalling determines the number of fast and slow myocytes. The distinct effects of Wnt5a and Wnt11 are consistent with their different expression patterns, which correlate with the ultimate distribution of slow and fast fibres in the wing. Overexpression of activated calmodulin kinase II mimics the effect of Wnt5a, suggesting that it uses this pathway. Finally, we show that overexpression of the Wnt antagonist Sfrp2 and DeltaLef1 reduces the number of myocytes. In Sfrp2-infected limbs, the number of Pax3 expressing cells was increased, suggesting that Sfrp2 blocks myogenic differentiation. Therefore, Wnt signalling modulates both the number of terminally differentiated myogenic cells and the intricate slow/fast patterning of the limb musculature.

Animals↗
PubMed2002

Caveolin expression during chondrogenesis in the avian limb.

Caveolin is the principal component and critical structural and functional element of caveolae, omega-shaped plasmalemmal invaginations, which have been implicated in a wide range of cellular processes in several different tissues. In the present study, we have investigated both the spatial and temporal expression of caveolin proteins during chondrogenesis in the avian tibiotarsus at days 10-20 of embryonic development. By using semiquantitative Western blotting, we found that caveolin-1 was clearly expressed in developing avian cartilage. The positive expression of caveolin-1 in cartilage showed an upward trend of accumulation temporally, with the highest levels of expression at 20 days of development. By using immunocytochemistry, we detected all three caveolin proteins in the cells of the outer fibrous articular surface, although caveolin-1 demonstrated the strongest and most consistent reactivity. In all cases, however, immunoreactivity appeared to be concentrated in cells facing the articular cavity. In the epiphyseal cartilage, immunocytochemistry revealed that caveolin-1 was present in the majority of chondrocytes within all layers of the cartilage and at all stages examined. A discrete, intense band of caveolin-1 immunoreactivity was apparent within the layer of flattened cells immediately underlying the proliferating rounded chondrocytes and suggests that caveolin-1 might be involved in regulating the progression of cells through these gradually maturing cell layers. In contrast to the results for caveolin-1, in the case of caveolin-2 and -3, chondrocytes were devoid of immunoreactivity in all regions of the epiphyseal cartilage. Overall, this study demonstrates that caveolin-1, -2, and -3 are expressed during chondrogenesis in the developing avian limb, although the patterns of expression are restricted both spatially and temporally throughout the differentiating cell layers of the cartilage. The results suggest that caveolin proteins might play a differentiation-dependent role during avian chondrogenesis.

Animals↗
PubMed2002

Molecular and cellular mechanisms involved in the generation of fiber diversity during myogenesis.

Skeletal muscles have a characteristic proportion and distribution of fiber types, a pattern which is set up early in development. It is becoming clear that different mechanisms produce this pattern during early and late stages of myogenesis. In addition, there are significant differences between the formation of muscles in head and those found in rest of the body. Early fiber type differentiation is dependent upon an interplay between patterning systems which include the Wnt and Hox gene families and different myoblast populations. During later stages, innervation, hormones, and functional demand increasingly act to determine fiber type, but individual muscles still retain an intrinsic commitment to form particular fiber types. Head muscle is the only muscle not derived from the somites and follows a different development pathway which leads to the formation of particular fiber types not found elsewhere. This review discusses the formation of fiber types in both head and other muscles using results from both chick and mammalian systems.

Animals↗