J. Dev. Biol.2015, 3(4), 112-128; doi:10.3390/jdb3040112 - published 20 November 2015 Show/Hide Abstract
Abstract: PEDF is a secreted glycoprotein that is widely expressed by multiple organs. Numerous functional contributions have been attributed to PEDF with antiangiogenic, antitumor, anti-inflammatory, and neurotrophic properties among the most prominent. The discovery that null mutations in the PEDF gene results in Osteogenesis Imperfecta Type VI, a rare autosomal recessive bone disease characterized by multiple fractures, highlights a critical developmental function for this protein. This ultra-rare orphan disease has provided biological insights into previous studies that noted PEDF’s effects on various stem cell populations. In addition to bone development, PEDF modulates resident stem cell populations in the brain, muscle, and eye. Functional effects on human embryonic stem cells have also been demonstrated. An overview of recent advances in our understanding by which PEDF regulates stem cells and their potential clinical applications will be evaluated in this review.
J. Dev. Biol.2015, 3(4), 93-111; doi:10.3390/jdb3040093 - published 12 November 2015 Show/Hide Abstract
Abstract: Proper control of the temporal onset of cellular differentiation is critical for regulating cell lineage decisions and morphogenesis during development. Pbx homeodomain transcription factors have emerged as important regulators of cellular differentiation. We previously showed, by using antisense morpholino knockdown, that Pbx factors are needed for the timely activation of myocardial differentiation in zebrafish. In order to gain further insight into the roles of Pbx factors in heart development, we show here that zebrafish pbx4 mutant embryos exhibit delayed onset of myocardial differentiation, such as delayed activation of tnnt2a expression in early cardiomyocytes in the anterior lateral plate mesoderm. We also observe delayed myocardial morphogenesis and dysmorphic patterning of the ventricle and atrium, consistent with our previous Pbx knock-down studies. In addition, we find that pbx4 mutant larvae have aberrant outflow tracts and defective expression of the proepicardial marker tbx18. Finally, we present evidence for Pbx expression in cardiomyocyte precursors as well as heterogeneous Pbx expression among the pan-cytokeratin-expressing proepicardial cells near the developing ventricle. In summary, our data show that Pbx4 is required for the proper temporal activation of myocardial differentiation and establish a basis for studying additional roles of Pbx factors in heart development.
J. Dev. Biol.2015, 3(3), 90-92; doi:10.3390/jdb3030090 - published 23 September 2015 Show/Hide Abstract
Abstract: While non-blood cell lineage has been studied for decades by developmental biologists, only recently has it been considered in disease. This is partly due to a lack of suitable reagents in experimental models, but it is also the result of a failure to understand the ability of cells to move or differentiate in pathological environments. This Editorial gives a quick overview of the Special Issue “Cell Fate Decisions in Development and Disease” and underscores the importance of understanding the mechanisms of cell fate determination and lineage.
J. Dev. Biol.2015, 3(2), 71-89; doi:10.3390/jdb3020071 - published 12 May 2015 Show/Hide Abstract
Abstract: Cartilage regeneration is massive during tail regeneration in lizards but little is known about cartilage regeneration in other body regions of the skeleton. The recovery capability of injured epiphyses of femur and tibia of lizard knees has been studied by histology and 5BrdU immunohistochemistry in lizards kept at high environmental temperatures. Lizard epiphyses contain a secondary ossified center of variable extension surrounded peripherally by an articular cartilage and basally by columns of chondrocytes that form the mataphyseal or growth plate. After injury of the knee epiphyses, a broad degeneration of the articular cartilage during the first days post-injury is present. However a rapid regeneration of cartilaginous tissue is observed from 7 to 14 days post-injury and by 21 days post-lesions, a large part of the epiphyses are reformed by new cartilage. Labeling with 5BrdU indicates that the proliferating cells are derived from both the surface of the articular cartilage and from the metaphyseal plate, two chondrogenic regions that appear proliferating also in normal, uninjured knees. Chondroblasts proliferate by interstitial multiplication forming isogenous groups with only a scant extracellular matrix that later increases. The high regenerative power of lizard articular cartilage appears related to the permanence of growing cartilaginous centers in the epiphyses of long bones such as those of the knee during adulthood. It is likely that these regions contain resident stem cells that give rise to new chondroblasts of the articular and metaphyseal cartilage during most of the lizard’s lifetime, but can produce an excess of cartilaginous tissues when stimulated by the lesion.
J. Dev. Biol.2015, 3(2), 57-70; doi:10.3390/jdb3020057 - published 27 April 2015 Show/Hide Abstract
Abstract: Since skin is the first barrier separating the body from the external environment, impaired wound healing can be life threatening to living organisms. Delayed healing processes are observed in animals under certain circumstances, such as advanced age, diabetes, and immunosuppression, but the underlying mechanisms of the abnormality remain elusive. Redox homeostasis is defined as the balance between the levels of reactive oxygen species (ROS) and antioxidants in which antioxidative enzymes play central roles in scavenging ROS. In addition to deleterious effects, ROS also exert beneficial functions on some cellular processes such as transducing phosphorylation signaling, but excessive antioxidants may impede the healing process. Hence, strict control over the amounts of antioxidants is desirable when applied for therapeutic purposes. Here we overview recent findings regarding the relationships between antioxidative enzymes and wound healing. Unveiling the role of antioxidative enzymes is expected to contribute to our understanding of the wound healing processes.
J. Dev. Biol.2015, 3(2), 25-56; doi:10.3390/jdb3020025 - published 20 April 2015 Show/Hide Abstract
Abstract: Retinoic acid (RA) is an important signaling molecule in the development of the endoderm and an important molecule in protocols used to generate endodermal cell types from stem cells. In this review, we describe the RA signaling pathway and its role in the patterning and specification of the extra embryonic endoderm and different endodermal organs. The formation of endoderm is an ancient evolutionary feature and RA signaling appears to have coevolved with the vertebrate lineage. Towards that end, we describe how RA participates in many regulatory networks required for the formation of extraembryonic structures as well as the organs of the embryo proper.