Plate Border Research Articles

Assessment of nail unit structures by ultrasound in patients with psoriatic arthritis and their correlations with disease activity indices: a case-control study.

Ultrasound (USG) of nail was performed to assess, (1) morphological alterations of nail plates in psoriatic arthritis (PsA) patients, (2) differences of nail unit parameters [nail bed thickness (NBT), nail matrix thickness (NMT) and nail plate distance (NPD)] in PsA patients from healthy controls (3) correlation of nail unit parameters with PsA disease activity indices. Total of 895 fingernails (448 nails of 45 PsA patients and 447 of 45 controls) were evaluated by USG. Psoriasis Area and Severity Index (PASI), Disease Activity in Psoriatic Arthritis (DAPSA), and Nail Psoriasis Severity Index (NAPSI) were calculated in PsA patients. Nail unit parameters were compared between two study groups. Correlation study was done between nail unit parameters and disease activity indices. All PsA patients showed ultrasound evidence of nail plate changes (87.95% of the total fingernails and 75.34% of the clinically normal nails). Loosening of the ventral nail plate border was most common (51.79%). Mean NBT (PsA: 0.19 ± 0.035cm, control: 0.17 ± 0.018cm, p = 0.003) and mean NMT (PsA: 0.32 ± 0.041cm, control: 0.28 ± 0.031cm, p = < 0.0001) were significantly increased in the PsA patients. Moderately positive correlation was observed between NAPSI score and mean NMT (Spearman r = 0.411, 95% confidence interval: 0.125-0.634, p = 0.005). USG evidence of nail plate alterations was frequent among PsA patients, even in clinically normal nails. Increased mean nail bed and matrix thickness were noted in PsA patients. Mean NMT had a moderately positive correlation with NAPSI score.

Mammalian embryos show metabolic plasticity toward the surrounding environment during neural tube closure.

Developing embryos rewire energy metabolism for developmental processes. However, little is known about how metabolic rewiring is coupled with development in a spatiotemporal manner. Here, we show that mammalian embryos display plasticity of glucose metabolism in response to the extracellular environment at the neural tube closure (NTC) stage, when the intrauterine environment changes upon placentation. To study how embryos modulate their metabolic state upon environmental change, we analyzed the steady-state level of ATP upon exposure to extrauterine environments using both an enzymatic assay and a genetically encoded ATP sensor. Upon environmental changes, NTC-stage embryos exhibited increased ATP content, whereas embryos before and after NTC did not. The increased ATP in the NTC-stage embryos seemed to depend on glycolysis. Intriguingly, an increase in mitochondrial membrane potential (ΔΨm) was also observed in the neural ectoderm (NE) and the neural plate border of the non-neural ectoderm (NNE) region. This implies that glycolysis can be coupled with the TCA cycle in the NE and the neural plate border depending on environmental context. Disrupting ΔΨm inhibited folding of the cranial neural plate. Thus, we propose that embryos tune metabolic plasticity to enable coupling of glucose metabolism with the extracellular environment at the NTC stage.

The b-HLH transcription factor Hes3 participates in neural plate border formation by interfering with Wnt/β-catenin signaling

Hes3 belongs to the Hes basic helix-loop-helix family of transcriptional repressors that play central roles in maintaining progenitor cells and regulating binary cell fate decisions in the embryo. During Xenopus laevis development, hes3 is expressed in the embryonic ectoderm in a horseshoe shape domain at the edge of the developing neural pate. Hes3 mis-expression at early neurula stage blocks neural crest (snai2, sox8, sox9 and sox10) and cranial placode (six1 and dmrta1) gene expression, and promotes neural plate (sox2 and sox3) fate. At tailbud stage, these embryos exhibited a massive up-regulation of both sox8 and sox10 expression, associated with an increase in genes important for melanocytes differentiation (mitf and dct). Using a hormone inducible construct we show that Hes3 does not induce a pigment cell differentiation program de novo, rather it maintains progenitor cells in an undifferentiated state, and as Hes3 expression subsides overtime these cells adopt a pigment cell fate. We demonstrate that mechanistically Hes3 mediates its activity through inhibition of Wnt/β-catenin signaling, a molecular pathway critical for neural crest specification and pigment cell lineage differentiation. We propose that Hes3 at the edge of the neural plate spatially restricts the response to mesoderm-derived Wnt ligands, thereby contributing to the establishment of sharp boundaries of gene expression at the neural plate border.

A gene regulatory network underlying the formation of pre-placodal ectoderm in Xenopus laevis

BackgroundThe neural plate border ectoderm gives rise to key developmental structures during embryogenesis, including the neural crest and the preplacodal ectoderm. Many sensory organs and ganglia of vertebrates develop from cranial placodes, which themselves arise from preplacodal ectoderm, defined by expression of transcription factor Six1 and its coactivator Eya1. Here we elucidate the gene regulatory network underlying the specification of the preplacodal ectoderm in Xenopus, and the functional interactions among transcription factors that give rise to this structure.ResultsTo elucidate the gene regulatory network upstream of preplacodal ectoderm formation, we use gain- and loss-of-function studies to explore the role of early ectodermal transcription factors for establishing the preplacodal ectoderm and adjacent ectodermal territories, and the role of Six1 and Eya1 in feedback regulation of these transcription factors. Our findings suggest that transcription factors with expression restricted to ventral (non-neural) ectoderm (AP2, Msx1, FoxI1, Vent2, Dlx3, GATA2) and those restricted to dorsal (neural) ectoderm (Pax3, Hairy2b, Zic1) are required for specification of both preplacodal ectoderm and neural crest in a context-dependent fashion and are cross-regulated by Eya1 and Six1.ConclusionThese findings allow us to elucidate a detailed gene regulatory network at the neural plate border upstream of preplacodal ectoderm formation based on functional interactions between ectodermal transcription factors. We propose a new model to explain the formation of immediately juxtaposed preplacodal ectoderm and neural crest territories at the neural plate border, uniting previous models.

Intracellular attenuation of BMP signaling via CKIP-1/Smurf1 is essential during neural crest induction.

The neural crest is induced at the neural plate border during gastrulation by combined bone morphogenetic protein (BMP), fibroblast growth factor (FGF), and Wnt signaling. While intermediate BMP levels are critical for this induction, secreted BMP inhibitors are largely absent from the neural plate border. Here, we propose a morphogen model in which intracellular attenuation of BMP signaling sets the required intermediate levels to maintain neural crest induction. We show that the scaffold protein casein kinase interacting protein 1 (CKIP-1) and ubiquitin ligase Smad ubiquitin regulatory factor 1 (Smurf1) are coexpressed with BMP4 at the chick neural plate border. Knockdown of CKIP-1 during a critical period between gastrulation and neurulation causes neural crest loss. Consistent with specific BMP modulation, CKIP-1 loss suppresses phospho-Smads 1/5/8 (pSmad1/5/8) and BMP reporter output but has no effect on Wnt signaling; Smurf1 overexpression (OE) acts similarly. Epistasis experiments further show that CKIP-1 rescues Smurf1-mediated neural crest loss. The results support a model in which CKIP-1 suppresses Smurf1-mediated degradation of Smads, uncovering an intracellular mechanism for attenuation of BMP signaling to the intermediate levels required for maintenance of neural crest induction.

Mechanics-guided developmental fate patterning.

A micropatterned human pluripotent stem cell-based developmental model was utilized to demonstrate the role of biophysical cues such as cell size and cytoskeletal contractile forces in directing patterning of neuroepithelial and neural plate border cells.

Mechanics-guided embryonic patterning of neuroectoderm tissue from human pluripotent stem cells.

Classic embryological studies have successfully applied genetics and cell biology principles to understand embryonic development. However, it remains unresolved how mechanics, as an integral driver of development, is involved in controlling tissue-scale cell fate patterning. Here we report a micropatterned human pluripotent stem (hPS)-cell-based neuroectoderm developmental model, in which pre-patterned geometrical confinement induces emergent patterning of neuroepithelial and neural plate border cells, mimicking neuroectoderm regionalization during early neurulation in vivo. In this hPS-cell-based neuroectoderm patterning model, two tissue-scale morphogenetic signals-cell shape and cytoskeletal contractile force-instruct neuroepithelial/neural plate border patterning via BMP-SMAD signalling. We further show that ectopic mechanical activation and exogenous BMP signalling modulation are sufficient to perturb neuroepithelial/neural plate border patterning. This study provides a useful microengineered, hPS-cell-based model with which to understand the biomechanical principles that guide neuroectoderm patterning and hence to study neural development and disease.

Regulation of neural crest development by the formin family protein Daam1

The neural crest (NC) multipotent progenitor cells form at the neural plate border and migrate to diverse locations in the embryo to differentiate into many cell types. NC is specified by several embryonic pathways, however the role of noncanonical Wnt signaling in this process remains poorly defined. Daam1 is a formin family protein that is present in embryonic ectoderm at the time of NC formation and can mediate noncanonical Wnt signaling. Our interference experiments indicated that Daam1 is required for NC gene activation. To further study the function of Daam1 in NC development we used a transgenic reporter Xenopus line, in which GFP transcription is driven by sox10 upstream regulatory sequences. The activation of the sox10:GFP reporter in a subset of NC cells was suppressed after Daam1 depletion and in embryos expressing N-Daam1, a dominant interfering construct. Moreover, N-Daam1 blocked reporter activation in neuralized ectodermal explants in response to Wnt11, but not Wnt8 or Wnt3a, confirming that the downstream pathways are different. In complementary experiments, a constitutively active Daam1 fragment expanded the NC territory, but this gain-of-function activity was eliminated in a construct with a point mutation in the FH2 domain that is critical for actin polymerization. These observations suggest a new role of Daam1 and actin remodeling in NC specification.

In vitro Inhibition of Soilborn Phytopathogens Treated With Swine Wastewater

Swine wastewater (SWW) is a residue from pig farming that presents a high load of nutrients and organic matter. The appliance of organic matter in soil alters the microbial dynamic and may suppress soilborn phytopathogens. This study aimed at evaluating the inhibition on mycelial growth of Sclerotinia sclerotiorum and Sclerotium rolfsii in vitro under SWW doses. Hereupon, three kilograms of a soil classified as red dystroferric latosol was collected and sieved. Half of it was autoclaved. SWW was incorporated at doses of 0 mL, 2.5 mL, 5 mL, 10 mL and 20 mL in both soil conditions, autoclaved and not autoclaved. Afterwards, 130 grams of each soil was separately put into Petri plates above what a thin layer (≅ 5 mL) of Water-Agar (2%) medium was carefully spread over. Above this agar layer, one disk (6 mm diameter) of pure mycelium from each fungal grown in Potato Dextrose Agar medium was individually placed on the center of each plate. Daily evaluations on mycelial growth measuring were taken and ended when mycelium in control plates (without SWW addition) reached plate borders. Results indicated that in autoclaved soil condition, the inhibition was proportional to the dose, what is to say that the higher the dose the less the mycelial growth. In not autoclaved soil there was no significant difference among treatments, suggesting stimuli on suppression effect for both pathogens caused by SWW. In addition, the confirmed potential of SWW as a suppressor of S. sclerotiorum and S. rolfsii leads to promising investigations on other phytopathogens hard to control.

A new transgenic Xenopus reporter line reveals dynamic expression of snail2 during cranial neural crest development

During vertebrate embryogenesis, the cranial neural crest (CNC) is induced at the neural plate border (NPB) and subsequently migrate and differentiate into various cells and tissues. In Xenopus, the transcription factor Snail2 is induced at the NPB by canonical Wnt signaling and is required for CNC induction and migration, but the roles of Snail2 at later stages remain unclear. To monitor CNC development in live embryos, we generated a transgenic X. tropicalis line expressing Green Fluorescent Protein(GFP) driven by the snail2 promoter. Using whole‐genome sequencing, we mapped the transgene insertion to a noncoding region. Live imaging of the transgenic embryos reveals that snail2 is expressed in pre‐migratory and migrating CNC but is lost in CNC cells that have arrived at their destinations. However, snail2 is re‐expressed during CNC differentiation in all CNC derivatives that were examined. Defects in CNC differentiation, in addition to induction and migration, can be readily detected using this transgenic snail2 reporter line. Finally, comparison with a transgenic Wnt reporter line shows that Wnt signaling is consistently activated prior to snail2 expression, suggesting that the Wnt‐Snail2 axis may play important roles in multiple stages of CNC development. We are also developing a new transgenic line with a photoconvertible protein instead of GFP that can be used to monitor cell fate of various CNC branches for lineage tracing of CNC derivatives.Support or Funding InformationFunded by: NIH DE022813 and GM114105This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.

Xenopus ADAM19 regulates Wnt signaling and neural crest specification by stabilizing ADAM13.

During vertebrate gastrulation, canonical Wnt signaling induces the formation of neural plate border (NPB). Wnt is also thought to be required for the subsequent specification of neural crest (NC) lineage at the NPB, but the direct evidence is lacking. We found previously that the disintegrin metalloproteinase ADAM13 is required for Wnt activation and NC induction in Xenopus Here, we report that knockdown of ADAM13 or its close paralog ADAM19 severely downregulates Wnt activity at the NPB, inhibiting NC specification without affecting earlier NPB formation. Surprisingly, ADAM19 functions nonproteolytically in NC specification by interacting with ADAM13 and inhibiting its proteasomal degradation. Ectopic expression of stabilized ADAM13 mutants that function independently of ADAM19 can induce the NC marker/specifier snail2 in the future epidermis via Wnt signaling. These results unveil the essential roles of a novel protease-protease interaction in regulating a distinct wave of Wnt signaling, which directly specifies the NC lineage.

Mice Expressing Myc in Neural Precursors Develop Choroid Plexus and Ciliary Body Tumors

Choroid plexus tumors and ciliary body medulloepithelioma are predominantly pediatric neoplasms. Progress in understanding the pathogenesis of these tumors has been hindered by their rarity and lack of models that faithfully recapitulate the disease. Here, we find that endogenous Myc proto-oncogene protein is down-regulated in the forebrain neuroepithelium, whose neural plate border domains give rise to the anterior choroid plexus and ciliary body. To uncover the consequences of persistent Myc expression, MYC expression was forced in multipotent neural precursors (nestin-Cre:Myc), which produced fully penetrant models of choroid plexus carcinoma and ciliary body medulloepithelioma. Nestin-mediated MYC expression in the epithelial cells of choroid plexus leads to the regionalized formation of choroid plexus carcinoma in the posterior domain of the lateral ventricle choroid plexus and the fourth ventricle choroid plexus that is accompanied by loss of multiple cilia, up-regulation of protein biosynthetic machinery, and hydrocephalus. Parallel MYC expression in the ciliary body leads also to up-regulation of protein biosynthetic machinery. Additionally, Myc expression in human choroid plexus tumors increases with aggressiveness of disease. Collectively, our findings expose a select vulnerability of the neuroepithelial lineage to postnatal tumorigenesis and provide a new mouse model for investigating the pathogenesis of these rare pediatric neoplasms.

Neural tube closure depends on expression of Grainyhead-like 3 in multiple tissues

Failure of neural tube closure leads to neural tube defects (NTDs), common congenital abnormalities in humans. Among the genes whose loss of function causes NTDs in mice, Grainyhead-like3 (Grhl3) is essential for spinal neural tube closure, with null mutants exhibiting fully penetrant spina bifida. During spinal neurulation Grhl3 is initially expressed in the surface (non-neural) ectoderm, subsequently in the neuroepithelial component of the neural folds and at the node-streak border, and finally in the hindgut endoderm. Here, we show that endoderm-specific knockout of Grhl3 causes late-arising spinal NTDs, preceded by increased ventral curvature of the caudal region which was shown previously to suppress closure of the spinal neural folds. This finding supports the hypothesis that diminished Grhl3 expression in the hindgut is the cause of spinal NTDs in the curly tail, carrying a hypomorphic Grhl3 allele. Complete loss of Grhl3 function produces a more severe phenotype in which closure fails earlier in neurulation, before the stage of onset of expression in the hindgut of wild-type embryos. This implicates additional tissues and NTD mechanisms in Grhl3 null embryos. Conditional knockout of Grhl3 in the neural plate and node-streak border has minimal effect on closure, suggesting that abnormal function of surface ectoderm, where Grhl3 transcripts are first detected, is primarily responsible for early failure of spinal neurulation in Grhl3 null embryos.

Neural induction by the node and placode induction by head mesoderm share an initial state resembling neural plate border and ES cells

Around the time of gastrulation in higher vertebrate embryos, inductive interactions direct cells to form central nervous system (neural plate) or sensory placodes. Grafts of different tissues into the periphery of a chicken embryo elicit different responses: Hensen's node induces a neural plate whereas the head mesoderm induces placodes. How different are these processes? Transcriptome analysis in time course reveals that both processes start by induction of a common set of genes, which later diverge. These genes are remarkably similar to those induced by an extraembryonic tissue, the hypoblast, and are normally expressed in the pregastrulation stage epiblast. Explants of this epiblast grown in the absence of further signals develop as neural plate border derivatives and eventually express lens markers. We designate this state as "preborder"; its transcriptome resembles embryonic stem cells. Finally, using sequential transplantation experiments, we show that the node, head mesoderm, and hypoblast are interchangeable to begin any of these inductions while the final outcome depends on the tissue emitting the later signals.

Znf703, a novel target of Pax3 and Zic1, regulates hindbrain and neural crest development in Xenopus.

The transcription factors Pax3 and Zic1 are critical to specify the neural plate border and to promote neural crest formation. In a microarray screen designed to identify genes regulated by Pax3 and Zic1 in Xenopus we isolated Znf703/Nlz1 a transcriptional repressor member of the NET (NocA/Nlz, Elbow, and TLP-1) protein family. At early neurula stage znf703 is expressed in the dorsal ectoderm, spanning the neural plate and neural plate border, with an anterior boundary of expression corresponding to rhombomeres 3 and 4 (r3/r4) in the prospective hindbrain. As a bonafide target of Pax3 and Zic1, znf703 is activated by neural plate border inducing signals, and its expression depends on Pax3 and Zic1 function in the embryo. Znf703 morpholino-mediated knockdown expanded several posterior hindbrain genes, while Znf703 overexpression completely obliterated the expression of these segmental genes, signifying that the transcriptional repressor activity of Znf703 is critical to pattern the hindbrain. Furthermore, snai2 and sox10 expression was severely impaired upon manipulation of Znf703 expression levels in the embryo suggesting that Znf703 participates in neural crest formation downstream of Pax3 and Zic1 in Xenopus.

Hypostomus velhochico, a new keeled Hypostomus Lacépède, 1803 (Siluriformes: Loricariidae) from the rio São Francisco basin in Brazil.

Hypostomus velhochico sp. n., is described from the rio São Francisco basin, in the states of Minas Gerais and Bahia, Brazil. The new species is mainly distinguished from its congeners by a combination of characters such as slender bicuspid teeth, dentaries angled more than 90 degrees, conspicuous keels along lateral series of plates, small roundish dark spots, one plate bordering supraoccipital, spots aligned along lateral series of plates, and by attaining small to medium size. Hypostomus velhochico is widespread in the rio São Francisco basin and has a more similar general pattern of external morphology to species from the Northeastern Brazilian Coastal drainages than to species of the rio São Francisco basin. Aspects about its ecology and its putative relationship are discussed.

ASSESSMENT OF OPTIMUM VALUE FOR DIP ANGLE AND LOCKING RATE PARAMETERS IN MAKRAN SUBDUCTION ZONE

Abstract. Makran subduction zone is one of the convergent areas that have been studied by spatial geodesy. Makran zone is located in the South Eastern of Iran and South of Pakistan forming the part of Eurasian-Arabian plate's border where oceanic crust in the Arabian plate (or in Oman Sea) subducts under the Eurasian plate ( Farhoudi and Karig, 1977). Due to lack of historical and modern tools in the area, a sampling of sparse measurements of the permanent GPS stations and temporary stations (campaign) has been conducted in the past decade. Makran subduction zone from different perspectives has unusual behaviour: For example, the Eastern and Western parts of the region have very different seismicity and also dip angle of subducted plate is in about 2 to 8 degrees that this value due to the dip angle in other subduction zone is very low. In this study, we want to find the best possible value for parameters that differs Makran subduction zone from other subduction zones. Rigid block modelling method was used to determine these parameters. From the velocity vectors calculated from GPS observations in this area, block model is formed. These observations are obtained from GPS stations that a number of them are located in South Eastern Iran and South Western Pakistan and a station located in North Eastern Oman. According to previous studies in which the locking depth of Makran subduction zone is 38km (Frohling, 2016), in the preparation of this model, parameter value of at least 38 km is considered. With this function, the amount of 2 degree value is the best value for dip angle but for the locking rate there is not any specified amount. Because the proposed model is not sensitive to this parameter. So we can not expect big earthquakes in West of Makran or a low seismicity activity in there but the proposed model definitely shows the Makran subduction layer is locked.

Top-Down Inhibition of BMP Signaling Enables Robust Induction of hPSCs Into Neural Crest in Fully Defined, Xeno-free Conditions.

SummaryDefects in neural crest development have been implicated in many human disorders, but information about human neural crest formation mostly depends on extrapolation from model organisms. Human pluripotent stem cells (hPSCs) can be differentiated into in vitro counterparts of the neural crest, and some of the signals known to induce neural crest formation in vivo are required during this process. However, the protocols in current use tend to produce variable results, and there is no consensus as to the precise signals required for optimal neural crest differentiation. Using a fully defined culture system, we have now found that the efficient differentiation of hPSCs to neural crest depends on precise levels of BMP signaling, which are vulnerable to fluctuations in endogenous BMP production. We present a method that controls for this phenomenon and could be applied to other systems where endogenous signaling can also affect the outcome of differentiation protocols.

Neural retina identity is specified by lens‐derived BMP signals

SummaryDuring early development of the CNS, the anterior neural domain becomes restricted into different regions as: the telencephalon, the optic cup and the diencephalon. Simultaneously, lens progenitors are specified in the neural plate border. The molecular mechanisms that regulate the induction and maintenance of eye‐field cells, and the specification of neural retina cells in relation to other forebrain domains have been poorly defined. If prospective lens cells affect the early development of retinal progenitors have been debated. We have analysed these issues in intact chick embryos and explant assays. Our results show that BMP signals emanating from the lens ectoderm maintain eye‐field identity, inhibit telencephalic character and induce neural retinal cells. This highlights a novel role for BMP signals during the early development of the retina that is distinct from previously described roles in dorso‐ventral patterning and fate choice between neural versus RPE cells. Our findings link the requirement of the lens ectoderm for neural retina specification with the molecular mechanism by which cells in the forebrain become specified as neural retina by BMP activity.

A chemical screen in zebrafish embryonic cells establishes that Akt activation is required for neural crest development.

The neural crest is a dynamic progenitor cell population that arises at the border of neural and non-neural ectoderm. The inductive roles of FGF, Wnt, and BMP at the neural plate border are well established, but the signals required for subsequent neural crest development remain poorly characterized. Here, we conducted a screen in primary zebrafish embryo cultures for chemicals that disrupt neural crest development, as read out by crestin:EGFP expression. We found that the natural product caffeic acid phenethyl ester (CAPE) disrupts neural crest gene expression, migration, and melanocytic differentiation by reducing Sox10 activity. CAPE inhibits FGF-stimulated PI3K/Akt signaling, and neural crest defects in CAPE-treated embryos are suppressed by constitutively active Akt1. Inhibition of Akt activity by constitutively active PTEN similarly decreases crestin expression and Sox10 activity. Our study has identified Akt as a novel intracellular pathway required for neural crest differentiation.