查看更多>>摘要：Macrophages are vital inhabitants of the developing heart. Nonetheless, their key role is not limited to prenatal processes, as embryo-derived macrophages govern the pool of cardiac macrophages also postnatally. Namely, embryonic cardiac macrophages are of yolk sac-, embryonic monocyte-, and heart-tissue origin. They persist, selfrenew and/or are gradually replaced by blood monocytes and assume microenvironment-dependent macrophage phenotypes both in the pre- and postnatal heart. Still, it is during embryonic development that cardiac macrophages gain tissue-specific phenotypes and multifunctional diverse properties. Currently, with the emergence of newer research methods, novel facts about embryonic macrophage ontogeny, lifecycle, and repertoire of functions have been revealed. Meeting the high interest in cardiac macrophages, we present this up-to-date overview of embryonic cardiac macrophages, emphasizing the fundamental concepts and discrepancies related to macrophage characteristics, current research gaps, and potential future developments in this field.
查看更多>>摘要：Planarians have a remarkable ability to undergo whole-body regeneration. Successful regeneration outcome is determined by processes like polarity establishment at the wound site, which is followed by pole (organizer) specification. Interestingly, these determinants are almost exclusively expressed by muscles in these animals. However, the molecular toolkit that enables the functional versatility of planarian muscles remains poorly understood. Here we report that SMED_DDX24, a D-E-A-D Box RNA helicase, is necessary for planarian survival and regeneration. We found that DDX24 is enriched in muscles and its knockdown disrupts muscle fiber organization. This leads to defective pole specification, which in turn results in misregulation of many positional control genes specifically during regeneration. ddx24 RNAi also upregulates wound-induced Wnt signalling. Suppressing this ectopic Wnt activity rescues the knockdown phenotype by enabling better anterior pole regeneration. To summarize, our work highlights the role of an RNA helicase in muscle fiber organization, and modulating amputationinduced wnt levels, both of which seem critical for pole re-organization, thereby regulating whole-body regeneration.
查看更多>>摘要：Developmental Biology embodies some of the most fundamental questions in Biology and can trace its roots back to several thousand years ago; the last 100 years have been particularly extraordinary. In part the advances have been fuelled by new technical advances and knowledge in many other areas, which have contributed to shaping the field as truly interdisciplinary. During those 100 years some of our predecessors identified some key questions and a few important principles especially by trying to find general rules that govern what cells are able to do and how they choose between different options, as well as principles of experimental design that can be used to uncover those rules even before we know their physicochemical underpinnings. But the field has been changing rapidly in the last two decades. Here I present a brief overview of some of the changes that have taken place over the last Century and a personal view of current directions. The picture that emerges is of some dark clouds on the horizon, so this is also a call to arms for our colleagues to try to regain what the field has been losing.
查看更多>>摘要：In the 20th century, developmental biology spearheaded a revolution in our understanding of complex biological problems. Its success rests in great part on a truly unique approach that has recruited a diversity of systems and research organisms rather than focusing on isolated cells or molecules, while also employing a wide variety of technological and intellectual approaches. But what will developmental biology contribute to this century? Advances in technology and instrumentation are presently moving at neck-breaking speed and herald the advent of an age of technological wonders in which previously inaccessible biology is now tangibly within our grasps. For instance, single-cell RNAseq has revealed novel, transient cell states in both stem and differentiated cells that are specified by defined changes in gene expression frequency during regeneration. Additionally, genome-wide epigenetic analyses combined with gene editing and transgenic methodologies have identified the existence of regeneration responsive enhancers in adult vertebrate tissues. These circumstances combined with our discipline's diversity of experimental and intellectual approaches offer unimaginable opportunities for developmental biologists not only to discover new biology but also to reveal entirely new principles of biology.
Piccolo, StefanoSladitschek-Martens, Hanna LucieCordenonsi, Michelangelo
14页
查看更多>>摘要：Myriads forces are at play during morphogenesis. Their concerted activity shapes individual cells, tissues and the whole embryo, representing the most awe-inspiring marvel of developmental biology. In spite of their prevalence, the potential instructive role of cell mechanics in fate determination and patterning has remained long neglected, in part due to the difficulties in translating the physical world of cells in molecular terms. The recent discovery of the principles of mechanotransduction, of how these impact on gene expression, is however starting to change this scenario, making mechanotransduction finally amenable to experimental dissection through genetics, molecular and bioengineering approaches. Here we review this emerging field, and a series of discoveries that potently bring back cell mechanics at the centerstage of vertebrate developmental biology. We discuss the role of actomyosin contractility as integrating platform between morphogens, lateral inhibition and mechanosignaling. We also review data indicating that supracellular pulling forces, coupled with solid-to -fluid changes in the material contexture of embryonic fields, may act as overarching mechanical "organizers ". The evidence also indicates that a continuum of forces is what ultimately locks "self-organizing " movements with cell fate, from the earliest pre-implantation decisions to the fine details of organogenesis. Notably, similar mechanisms are reawakened in organoids and in adult tissues during regeneration. Developmental biology has been correctly depicted, but recently often forgotten, as the "mother " of all biological disciplines. Investigations in developmental mechanics may revamp interest, and have a broad impact in the fields of regenerative medicine, stem cells and cancer biology.
查看更多>>摘要：The morphogenesis and plasticity of dendritic spines are associated with synaptic strength, learning, and memory. Dendritic spines are highly compartmentalized structures, which makes proteins involved in cellular polarization and membrane compartmentalization likely candidates regulating their formation and maintenance. Indeed, recent studies suggest polarity proteins help form and maintain dendritic spines by compartmentalizing the spine neck and head. Here, we review emerging evidence that polarity proteins regulate dendritic spine plasticity and stability through the cytoskeleton, scaffolding molecules, and signaling molecules. We specifically analyze various polarity complexes known to contribute to different forms of cell polarization processes and examine the essential conceptual context linking these groups of polarity proteins to dendritic spine morphogenesis, plasticity, and cognitive functions.
Wang, RuiDuBuc, Timothy Q.Steele, Robert E.Collins, Eva-Maria S....
7页
查看更多>>摘要：We present a new transgenic Hydra vulgaris line expressing a distinct fluorescent protein in each of the three cell lineages of the adult polyp. Plasmid microinjection was used to generate a novel transgenic Hydra line expressing the yellow fluorescent protein YPet in the ectodermal epithelial cell lineage. Tissue grafting was then used to combine a YPet animal with a line that expresses DsRed2 in the endodermal epithelial lineage and eGFP in the interstitial cell (i-cell) lineage. The resulting triple-labeled ("tricolored") transgenic line provides, for the first time, a Hydra in which all three cell lineages can be imaged simultaneously in vivo. We show example confocal images of whole animals and individual cells to illustrate the imaging capabilities that this new line makes possible. We also used this line to carry out new studies of cell fate in the tentacles. Specifically, we evaluated the well-accepted notion that all tentacle cells are terminally differentiated and are displaced or migrate exclusively towards the distal end of the tentacle. We found that ectodermal and endodermal epithelial cells are displaced distally, as expected. In contrast, members of the i-cell lineage, which resembled neuronal precursors, could migrate out of a tentacle into the body column. This example illustrates how this tricolored transgenic line enables new in vivo studies of cell behaviors in Hydra.
查看更多>>摘要：Pre-placodal ectoderm (PPE), a horseshoe-shaped narrow region formed during early vertebrate development, gives rise to multiple types of sensory organs and ganglia. For PPE induction, a certain level of FGF signal acti-vation is required. However, it is difficult to reproducibly induce the narrow region with variations in gene expression, including FGF, among individuals. An intracellular regulatory factor of FGF signaling, Dusp6, is expressed by FGF signal activation and inactivates a downstream regulator, ERK1/2, in adult tissues; however, its role in early development is not well known. Here, we reveal that Dusp6 is expressed in an FGF-dependent manner in Xenopus PPE. Gain-and loss-of-function experiments showed that Dusp6 is required for expression of a PPE gene, Six1, and patterning of adjacent regions, neural plate, and neural crest. To reveal the importance of Dusp6 in variable FGF production, we performed Dusp6 knockdown with FGF-bead implantation, which resulted in varying Six1 expression patterns. Taken together, these results suggest that Dusp6 is required for PPE formation and that it contributes to the robust patterning of PPE by mediating FGF signaling.
查看更多>>摘要：The Drosophila BMP 2/4 homologue Decapentaplegic (Dpp) acts as a morphogen to regulate diverse developmental processes, including wing morphogenesis. Transcriptional feedback regulation of this pathway ensures tightly controlled signaling outputs to generate the precise pattern of the adult wing. Nevertheless, few direct Dpp target genes have been explored and our understanding of feedback regulation remains incomplete. Here we employ transcriptional profiling following dpp conditional knockout to identify nord, a novel Dpp/BMP feedback regulator. nord mutants generated by CRISPR/Cas9 mutagenesis produce a smaller wing and display low penetrance venation defects. At the molecular level, nord encodes a secreted heparin-binding protein, and we show that its overexpression is sufficient to antagonize Dpp/BMP signaling. Mechanistically, we demonstrate that Nord physically interacts with the Dpp/BMP co-receptor Dally and promotes its degradation. In sum, we propose that Nord fine-tunes Dpp/BMP signaling by regulating Dally availability on the cell surface, with implications for both developmental and disease models.
NSTL
Elsevier