Animal organs are typically formed during embryogenesis by following one specific developmental programme. Here, we report that neuromast organs are generated by two distinct and sequential programmes that result in parallel sensory lines in medaka embryos. A ventral posterior lateral line (pLL) is composed of neuromasts deposited by collectively migrating cells whereas a midline pLL is formed by individually migrating cells. Despite the variable number of neuromasts among embryos, the sequential programmes that we describe here fix an invariable ratio between ventral and midline neuromasts. Mechanistically, we show that the formation of both types of neuromasts depends on the chemokine receptor genes cxcr4b and cxcr7b, illustrating how common molecules can mediate different morphogenetic processes. Altogether, we reveal a self-organising feature of the lateral line system that ensures a proper distribution of sensory organs along the body axis.
Moderate and severe clozapine intoxications can already occur after ingestion of doses in the low therapeutic range, especially in patients older than 50 years. Poisoned patients have to be monitored for central nervous system depression, tachycardia, blood pressure abnormalities, respiratory depression, and QTc prolongation.
1Most organs rely on stem cells to maintain homeostasis during post-embryonic life. Typically, stem 2 cells of independent lineages work coordinately within mature organs to ensure proper ratios of cell 3 types. Little is known, however, on how these different stem cells locate to forming organs during 4 development. Here we show that neuromasts of the posterior lateral line in medaka are composed of 5 two independent life-long lineages with different embryonic origins. Clonal analysis and 4D 6 imaging revealed a hierarchical organisation with instructing and responding roles: an inner, neural 7 lineage induces the formation of an outer, border cell lineage (nBC) from the skin epithelium. Our 8 results demonstrate that the neural lineage is necessary and sufficient to generate nBCs highlighting 9 self-organisation principles at the level of the entire embryo. We hypothesise that transformation of 10 surrounding tissues plays a major role during the establishment of vertebrate stem cell niches. 11 * Seleit, Krämer et al, Figure 8
Most organs rely on stem cells to maintain homeostasis during post-embryonic life. Typically, stem cells of independent lineages work coordinately within mature organs to ensure proper ratios of cell types. Little is known, however, on how these different stem cells locate to forming organs during development. Here we show that neuromasts of the posterior lateral line in medaka are composed of two independent life-long lineages with different embryonic origins. Clonal analysis and 4D imaging revealed a hierarchical organisation with instructing and responding roles: an inner, neural lineage induces the formation of an outer, border cell lineage (nBC) from the skin epithelium. Our results demonstrate that the neural lineage is necessary and sufficient to generate nBCs highlighting self-organisation principles at the level of the entire embryo. We hypothesise that induction of surrounding tissues plays a major role during the establishment of vertebrate stem cell niches.
Objective S100A6, a member of the S100-protein family, has been described as relevant for cell cycle entry and progression in endothelial cells (ECs). The molecular mechanism conferring S100A6’s proliferative actions, however, remained elusive. Approach and Results Originating from the clinically relevant observation of enhanced S100A6 protein expression in proliferating ECs in remodeling coronary and carotid arteries, our study unveiled S100A6 as a suppressor of antiproliferative signal transducers and activators of transcription 1 (STAT1) signaling. Discovery of the molecular liaison was enabled by combining gene expression time series analysis with bioinformatic pathway modeling in S100A6 silenced human ECs stimulated with vascular endothelial growth factor A (VEGF-A). This unbiased approach led to successful identification and experimental validation of interferon-inducible transmembrane protein 1 (IFITM1) and protein inhibitors of activated STAT (PIAS) as key components of the link between S100A6 and STAT1. Conclusions Given the important role of coordinated EC cell cycle activity for integrity and reconstitution of the inner lining of arterial blood vessels in health and disease, STAT1 suppression by S100A6 may represent a promising therapeutic target to facilitate reendothelialization in damaged vessels.
Mammals display a species-specific number, size and location of organs exclusively built during embryogenesis. In fish and amphibians, however, organs must adapt to life-long growth either by expanding in size and/or increasing in number. Here we use neuromasts, small sensory organs that increase in number as fish grow in size, to explore organogenesis during post-embryonic stages. Using iterative imaging, we reveal that post-embryonic organogenesis in the medaka caudal-neuromast-cluster (CNC) is mediated by organ-founder stem cells that delaminate from a functional neuromast. Organ-founder stem cells undergo epithelial-to-mesenchymal (EMT) transition as shown by molecular markers and cellular rearrangements. Chemokine signaling controls the dynamics of organ-founder stem cell delamination, which occurs at a stereotypic position that endures experimental and genetic perturbations. 2-photon laser ablation experiments reveal that organ-founder stem cells are rapidly reconstituted and suggest that these do not constitute a pre-defined population but are rather specified in situ. Our findings contribute to better understanding physiological stem-cell mediated organogenesis, a growth strategy present in life-long growing vertebrates. We speculate that a similar strategy could operate in vertebrates with determined-size as a template for pathological conditions like metastasis, where cells detach from their original organ and expand remotely.
Although Edward Jenner applied the first vaccines by scratching cow pox material into the skin, the profound immunological properties of the skin have become evident through research and discoveries only in the last 20 years. The immunological cells in the epidermis and the dermis are suitable targets for transcutaneous vaccination and immunotherapy. However, as the skin represents a natural barrier for topically administered large molecules, novel methods to overcome this barrier function have been described. There are chemical, biochemical and physical methods, many of which are pain-free and therefore especially suitable for children. Also for adults non-invasive methods of vaccination and immunotherapy are attractive as self-administration is feasible. Future products are currently undergoing clinical tests which provide promising results.
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