J. Dev. Biol.2014, 2(4), 210-229; doi:10.3390/jdb2040210 (registering DOI) - published 19 December 2014 Show/Hide Abstract
Abstract: The lumbar spinal cords of lizards were transected, but after the initial paralysis most lizards recovered un-coordinated movements of hind limbs. At 25-45 days post-lesion about 50% of lizards were capable of walking with a limited coordination. Histological analysis showed that the spinal cord was transected and the ependyma of the central canal formed two enlargements to seal the proximal and distal ends of the severed spinal cord. Glial and few small neurons were formed while bridge axons crossed the gap between the proximal and the distal stumps of the transected spinal cord as was confirmed by retrograde tract-tracing technique. The bridging fibers likely derived from interneurons located in the central and dorsal grey matter of the proximal spinal cord stump suggesting they belong to the local central locomotory pattern generator circuit. The limited recovery of hind limb movements may derive from the regeneration or sprouting of short proprio-spinal axons joining the two stumps of the transected spinal cord. The present observations indicate that the study on spinal cord regeneration in lizards can give insights on the permissive conditions that favor nerve regeneration in amniotes.
J. Dev. Biol.2014, 2(4), 198-209; doi:10.3390/jdb2040198 (registering DOI) - published 19 December 2014 Show/Hide Abstract
Abstract: Wound healing is a well-orchestrated process, with various cells and growth factors coming into the wound bed at a specific time to influence the healing. Understanding the wound healing process is essential to generating wound healing products that help with hard-to-heal acute wounds and chronic wounds. The 2D scratch assay whereby a wound is created by scratching a confluent layer of cells on a 2D substrate is well established and used extensively but it has a major limitation—it lacks the complexity of the 3D wound healing environment. Established 3D wound healing models also have many limitations. In this paper, we present a novel 3D wound healing model that closely mimics the skin wound environment to study the cell migration of fibroblasts and keratinocytes. Three major components that exist in the wound environment are introduced in this new model: collagen, fibrin, and human foreskin fibroblasts. The novel 3D model consists of a defect, representing the actual wound, created by using a biopsy punch in a 3D collagen construct. The defect is then filled with collagen or with various solutions of fibrinogen and thrombin that polymerize into a 3D fibrin clot. Fibroblasts are then added on top of the collagen and their migration into the fibrin—or collagen—filled defect is followed for nine days. Our data clearly shows that fibroblasts migrate on both collagen and fibrin defects, though slightly faster on collagen defects than on fibrin defects. This paper shows the visibility of the model by introducing a defect filled with fibrin in a 3D collagen construct, thus mimicking a wound. Ongoing work examines keratinocyte migration on the defects of a 3D construct, which consists of collagen-containing fibroblasts. The model is also used to determine the effects of various growth factors, delivered in the wound defects, on fibroblasts’ and keratinocytes’ migration into the defects. Thus this novel 3D wound healing model provides a more complex wound healing assay than existing wound models.
J. Dev. Biol.2014, 2(3), 174-197; doi:10.3390/jdb2030174 - published 26 June 2014 Show/Hide Abstract
Abstract: Retinoic acid signaling is required at several steps during the development of the spinal cord, from the specification of generic properties to the final acquisition of neuronal subtype identities, including its role in trunk neural crest development. These functions are associated with the production of retinoic acid in specific tissues and are highly dependent on context. Here, we review the defects associated with retinoic acid signaling manipulations, mostly in chick and mouse models, trying to separate the different processes where retinoic acid signaling is involved and to highlight common features, such as its ability to promote transitions along the neuronal differentiation cascade.
J. Dev. Biol.2014, 2(3), 158-173; doi:10.3390/jdb2030158 - published 26 June 2014 Show/Hide Abstract
Abstract: Retinoids function as important regulatory signaling molecules during development, acting in cellular growth and differentiation both during embryogenesis and in the adult animal. In 1953, Fell and Mellanby first found that excess vitamin A can induce transdifferentiation of chick embryonic epidermis to a mucous epithelium (Fell, H.B.; Mellanby, E. Metaplasia produced in cultures of chick ectoderm by high vitamin A. J. Physiol.1953, 119, 470–488). However, the molecular mechanism of this transdifferentiation process was unknown for a long time. Recent studies demonstrated that Gbx1, a divergent homeobox gene, is one of the target genes of all-trans retinoic acid (ATRA) for this transdifferentiation. Furthermore, it was found that ATRA can induce the epidermal transdifferentiation into a mucosal epithelium in mammalian embryonic skin, as well as in chick embryonic skin. In the mammalian embryonic skin, the co-expression of Tgm2 and Gbx1 in the epidermis and an increase in TGF-β2 expression elicited by ATRA in the dermis are required for the mucosal transdifferentiation, which occurs through epithelial-mesenchymal interaction. Not only does retinoic acid (RA) play an important role in mucosal transdifferentiation, periderm desquamation, and barrier formation in the developing mammalian skin, but it is also involved in hair follicle downgrowth and bending by its effect on the Wnt/β-catenin pathway and on members of the Runx, Fox, and Sox transcription factor families.
J. Dev. Biol.2014, 2(2), 138-157; doi:10.3390/jdb2020138 - published 29 April 2014 Show/Hide Abstract
Abstract: The precise coordination of cell death and cell differentiation during the formation of developing digits is essential for generating properly shaped limbs. Retinoic acid (RA) has a fundamental role in digit development; it promotes or inhibits the molecular expression of several critical genes. This control of gene expression establishes molecular cascades that enable both the commencement of cell death and the inhibition of cell differentiation. In this review, we focus on the antagonistic functions between RA and fibroblast growth factor (FGF) signaling in the control of cell death and between RA and transforming growth factor beta (TGFβ) signaling in the control of cell differentiation.
J. Dev. Biol.2014, 2(2), 117-137; doi:10.3390/jdb2020117 - published 23 April 2014 Show/Hide Abstract
Abstract: The discovery of stem and progenitor cells in the adult mammalian heart has added a vital dimension to the field of cardiac regeneration. Cardiac-resident stem cells are likely sequestered as reserve cells within myocardial niches during the course of embryonic cardiogenesis, although they may also be recruited from external sources, such as bone marrow. As we begin to understand the nature of cardiac-resident stem and progenitor cells using a variety of approaches, it is evident that they possess an identity embedded within their gene regulatory networks that favours cardiovascular lineage potential. In addition to contributing lineage descendants, cardiac stem cells may also be stress sensors, offering trophic cues to other cell types, including cardiomyocytes and vasculature cells, and likely other stem cells and immune cells, during adaptation and repair. This presents numerous possibilities for endogenous cardiac stem and progenitor cells to be used in cell therapies or as targets in heart rejuvenation. In this review, we focus on the epicardium as an endogenous source of multi-potential mesenchymal progenitor cells in development and as a latent source of such progenitors in the adult. We track the origin and plasticity of the epicardium in embryos and adults in both homeostasis and disease. In this context, we ask whether directed activation of epicardium-derived progenitor cells might have therapeutic application.