In Vivo Expression of EphrinA5-Fc in Mice Results in Cephalic Neural Crest Agenesis and Craniofacial Abnormalities

Eph receptors and their ligands ephrins have been implicated in guiding the directed migration of neural crest cells (NCCs). In this study, we found that Wnt1-Cre-mediated expression of ephrinA5-Fc along the dorsal midline of the dien- and mesencephalon resulted in severe craniofacial malformation of mouse embryo. Interestingly, expression of cephalic NCC markers decreased significantly in the frontonasal process and branchial arches 1 and 2, which are target areas for the migratory cephalic NCCs originating in the dien- and mesencephalon. In addition, these craniofacial tissues were much smaller in mutant embryos expressing ephrinA5-Fc. Importantly, EphA7-positive cephalic NCCs were absent along the dorsal dien- and mesencephalon of mutant embryos expressing ephrinA5-Fc, suggesting that the generation of cephalic NCCs is disrupted due to ephrinA5-Fc expression. NCC explant experiments suggested that ephrinA5-Fc perturbed survival of cephalic NCC precursors in the dorsal midline tissue rather than affecting their migratory capacity, which was consistent with our previous report that expression of ephrinA5-Fc in the dorsal midline is responsible for severe neuroepithelial cell apoptotic death. Taken together, our findings strongly suggest that expression of ephrinA5-Fc decreases a population of cephalic NCC precursors in the dorsal midline of the dien- and mesencephalon, thereby disrupting craniofacial development in the mouse embryos.     

Cell migration, pattern formation and cell fate during head development in lungfishes and amphibians

Summary In the evolution of land-living vertebrates, the transition from spending the entire life cycle in the water to first a biphasic (adult on land, eggs and larvae in water) and later a terrestrial life-history mode was achieved by changes in developmental processes and regulatory mechanisms. Lungfishes, salamanders and frogs are studied as examples of species which span this transition. The migration and fate of the embryonic cells that form the head is studied, using experimental embryology (extirpation and transplantation of cells), molecular markers and novel microscopy techniques — such as confocal microscopy. Knowing the migratory routes and fates of the cells that form head structures is important for an elucidation of the changes that took place e.g. when gill arches transformed into head cartilages, and when the specialised larval mouth structures present in today’s frogs and toads arose as an evolutionary innovation. Results so far indicate that the early migration and pattern formation of neural crest cells in the head region is surprisingly conserved. Both the amphibians investigated and the Australian lungfish have the same number of migrating neural crest streams, and the identity of the streams is preserved. The major difference lies in the timing of migration, where there has been a heterochronic shift such that cell migration starts much later in the Australian lungfish than in the amphibians. The molecular mechanisms regulating the formation of streams of cranial neural crest cells seem, at least in part, to be differential expression of ephrins and ephrin receptors, which mediate cell sorting. Our understanding of the behaviour of migrating cells (primarily the more well characterised neural crest cells) could be enhanced by a modelling approach. I present preliminary ideas on how this could be achieved, inspired by recent work on Dictyostelium development and our own previous work on pigment cells and their pattern formation during salamander embryogenesis.     

Evolutionary developmental studies of cyclostomes and the origin of the vertebrate neck

Because they lack some gnathostome-specific traits, cyclostomes have often been regarded as representing an intermediate state linking non-vertebrate chordates and gnathostomes. To understand the evolutionary origins of the jaw and paired fins, lamprey embryos and larvae have been used as comparative models. The lack of the jaw–neck region is a conspicuous feature specific to cyclostomes; however, the absence of these features has been largely neglected both in evolutionary developmental studies and in the field of classical comparative embryology. This review seeks to develop a possible evolutionary scenario of the vertebrate neck muscles by taking the cucullaris (trapezius) muscle as the focus. By combining the comparative embryology of lampreys and gnathostomes, and considering the molecular-level developmental mechanism of skeletal muscle differentiation, this review argues that the establishment of the vertebrate neck deserves to be called an evolutionary novelty based on the remodeling of mesenchymal components between the cranium and the shoulder girdle, which involves both mesodermal and neural crest cell lineages.     

Hox genes, neural crest cells and branchial arch patterning

Proper craniofacial development requires the orchestrated integration of multiple specialized tissue interactions. Recent analyses suggest that craniofacial development is not dependent upon neural crest pre-programming as previously thought but is regulated by a more complex integration of cell and tissue interactions. In the absence of neural crest cells it is still possible to obtain normal arch patterning indicating that neural crest is not responsible for patterning all of arch development. The mesoderm, endoderm and surface ectoderm tissues play a role in the patterning of the branchial arches, and there is now strong evidence that Hoxa2 acts as a selector gene for the pathways that govern second arch structures.     

Heterochrony revisited: the evolution of developmental sequences

The concept of heterochrony is a persistent component of discussions about the way that evolution and development interact. Since the late 1970s heterochrony has been defined largely as developmental changes in the relationship of size and shape. This approach to heterochrony, here termed growth heterochrony, is limited in the way it can analyse change in the relative timing of developmental events in a number of respects. In particular, analytical techniques do not readily allow the study of changes in developmental events not characterized by size and shape parameters, or of many kinds of events in many taxa. I discuss here an alternative approach to heterochrony, termed sequence heterochrony, in which a developmental trajectory is conceptualized as a series of discrete events. Heterochrony is demonstrated when the sequence position of an event changes relative to other events in that sequence. I summarize several analytical techniques that allow the investigation of sequence heterochrony in phylogenetic contexts and also quantitatively. Finally, several examples of how this approach may be used to test hypotheses on the way development evolves are summarized.     

Loss of floor plate Netrin-1 impairs midline crossing of corticospinal axons and leads to mirror movements

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Should I stay or should I go? Cadherin function and regulation in the neural crest

Our increasing comprehension of neural crest cell development has reciprocally advanced our understanding of cadherin expression, regulation, and function. As a transient population of multipotent stem cells that significantly contribute to the vertebrate body plan, neural crest cells undergo a variety of transformative processes and exhibit many cellular behaviors, including epithelial‐to‐mesenchymal transition (EMT), motility, collective cell migration, and differentiation. Multiple studies have elucidated regulatory and mechanistic details of specific cadherins during neural crest cell development in a highly contextual manner. Collectively, these results reveal that gradual changes within neural crest cells are accompanied by often times subtle, yet important, alterations in cadherin expression and function. The primary focus of this review is to coalesce recent data on cadherins in neural crest cells, from their specification to their emergence as motile cells soon after EMT, and to highlight the complexities of cadherin expression beyond our current perceptions, including the hypothesis that the neural crest EMT is a transition involving a predominantly singular cadherin switch. Further advancements in genetic approaches and molecular techniques will provide greater opportunities to integrate data from various model systems in order to distinguish unique or overlapping functions of cadherins expressed at any point throughout the ontogeny of the neural crest.