pinecone/core-2020-05-10-deduplication huggingface dataset:
Wingless Modulates the Effects of Dominant Negative Notch Molecules in the Developing Wing of Drosophila

AbstractThe development and patterning of the wing in Drosophila relies on a sequence of cell interactions molecularly driven by a number of ligands and receptors. Genetic analysis indicates that a receptor encoded by the Notch gene and a signal encoded by the wingless gene play a number of interdependent roles in this process and display very strong functional interactions. At certain times and places, during wing development, the expression of wingless requires Notch activity and that of its ligands Delta and Serrate. This has led to the proposal that all the interactions between Notch and wingless can be understood in terms of this regulatory relationship. Here we have tested this proposal by analysing interactions between Delta- and Serrate-activated Notch signalling and Wingless signalling during wing development and patterning. We find that the cell death caused by expressing dominant negative Notch molecules during wing development cannot be rescued by coexpressing Nintra. This suggests that the dominant negative Notch molecules cannot only disrupt Delta and Serrate signalling but can also disrupt signalling through another pathway. One possibility is the Wingless signalling pathway as the cell death caused by expressing dominant negative Notch molecules can be rescued by activating Wingless signalling. Furthermore, we observe that the outcome of the interactions between Notch and Wingless signalling differs when we activate Wingless signalling by expressing either Wingless itself or an activated form of the Armadillo. For example, the effect of expressing the activated form of Armadillo with a dominant negative Notch on the patterning of sense organ precursors in the wing resembles the effects of expressing Wingless alone. This result suggests that signalling activated by Wingless leads to two effects, a reduction of Notch signalling and an activation of Armadillo
Teneurins: A Novel Family of Neuronal Cell Surface Proteins in Vertebrates, Homologous to the Drosophila Pair-Rule Gene Product Ten-m

AbstractWe have characterized chicken teneurin-1 and teneurin-2, two homologues of the Drosophila pair-rule gene product Ten-m and Drosophila Ten-a. The high degree of conservation between the vertebrate and invertebrate proteins suggests that these belong to a novel family. We propose to name the vertebrate members of this family teneurins, because of their predominant expression in the nervous system. The expression of teneurin-1 and -2 was investigated by in situ hybridization. We show that teneurin-1 and -2 are expressed by distinct populations of neurons during the time of axonal growth. The most prominent site of expression of chicken teneurins is the developing visual system. Recombinant teneurin-2 was expressed to assay its molecular and functional properties. We show that it is a type II transmembrane protein, which can be released from the cell surface by proteolytic cleavage at a furin site. The expression of teneurin-2 in neuronal cells led to a significant increase in the number of filopodia and to the formation of enlarged growth cones. The expression pattern of teneurins in the developing nervous system and the ability of teneurin-2 to reorganize the cellular morphology indicate that these proteins may have an important function in the formation of neuronal connections
Redundant Enhancers Mediate Transcriptional Repression of AGAMOUS by APETALA2

AbstractThe floral homeotic gene AGAMOUS specifies stamen and carpel fate in the central whorls of Arabidopsis flowers. Transcription of AGAMOUS RNA is restricted to the center of developing flowers by several, partially redundant negative regulators, one of which is the homeotic gene APETALA2. We have identified regulatory elements that mediate transcriptional repression of AGAMOUS by APETALA2 and found that several redundant elements respond independently to loss of APETALA2 activity. Thus, redundancy at the level of cis-regulatory sequences is independent of redundancy at the level of trans-regulators. We have also found that only the early, but not the late, effects of APETALA2 on AGAMOUS require the meristem-identity protein LEAFY, a positive regulator of AGAMOUS
Hepatocyte Growth Factor (HGF) Receptor Expression and Role of HGF during Embryonic Mouse Testis Development

AbstractThe hepatocyte growth factor (HGF) receptor, c-met, transduces the HGF multiple biological activities. During embryonic development the system HGF/c-met regulates the morphogenesis of different organs and tissues. In this study we examined c-met gene expression during mouse testis development and, by means of Northern blot and in situ hybridization, we report the receptor expression pattern. C-met expression is not detectable in male genital ridges isolated from embryos at 11.5 days postcoitum (dpc). In testes isolated from 12.5 and 13.5 dpc, c-met expression is detectable and essentially localized in the developing cords. Male genital ducts do not express c-met at the reported ages, whereas female ducts appear c-met positive. Moreover, we report that HGF is able to induce testicular morphogenesis in vitro. Male genital ridges isolated from embryos at 11.5 dpc are morphologically nonorganized. Culturing 11.5 dpc urogenital ridges in the presence of HGF we obtained testis organization and testicular cord formation. Our data demonstrate that c-met is expressed during the beginning period of testis differentiation and that HGF is able to support testicular differentiation in vitro. All these data indicate that this growth factor, besides its role as mitogenic factor, plays a fundamental role during testicular cord formation probably inducing cell migration and/or cell differentiation
DNA-Binding Specificity and Embryological Function of Xom (Xvent-2)

AbstractXom (also known as Xvent-2) is a homeobox-containing gene expressed throughout the early gastrula of the Xenopus embryo with the exception of the organizer. Activation of Xom is an immediate-early response to BMP signaling, and overexpression of Xom, like overexpression of BMP family members, causes ventralization of the embryo. In this paper we first show that Xom is a transcriptional repressor and we then define its preferred DNA-binding site. Overexpression of wild-type Xom and a dominant-negative form suggests that Xom functions by repressing transcription of goosecoid, and analysis of the goosecoid promoter reveals a site which is required for Xom-mediated repression of goosecoid promoter reporter constructs. Together, these results suggest that Xom causes down-regulation of goosecoid in a direct fashion and that this accounts, at least in part, for the ability of Xom to cause ventralization of the Xenopus embryo
Goosecoid Regulates the Neural Inducing Strength of the Mouse Node

AbstractThe homeobox gene goosecoid was the first specific genetic marker of Spemann's organizer in vertebrate embryos to be discovered. In the frog, misexpression of this gene by RNA injection produces duplication of the posterior axis. For these reasons, the recent finding that mice lacking goosecoid function have no early axial defects was rather surprising. Here we assay the neural inducing strength of wild-type and goosecoid-mutant mouse nodes by transplantation into primitive streak stage chick embryos. Wild-type mouse nodes strongly induce the neural-specific transcription factors Sox2 and Sox3 in the chick host. Homozygous goosecoid−/− nodes are severely impaired in their ability to induce both genes. Heterozygous goosecoid+/− nodes induceSox3 as well as wild-type nodes, but resemble −/− nodes in their limited ability to induce Sox2. We propose that goosecoid does play a role in regulating the neural inducing strength of the node and that regulative mechanisms exist which mask the early phenotypic consequences of goosecoid mutations in the intact mouse embryo
Dorsoventral Patterning of the Telencephalon Is Disrupted in the Mouse Mutant extra-toesJ

AbstractLittle is known about the mechanisms that control the development of regional identity in the mammalian telencephalon. The Gli family of transcription factor genes is involved in the regulation of pattern at many sites in the embryo and is expressed in the embryonic mouse telencephalon. We have analyzed telencephalic patterning in the extra-toesJ (XtJ) mouse mutant, which carries a deletion in theGli family member Gli3. We report that dorsoventral patterning of the telencephalon is dramatically disrupted in the XtJ mutant. Specific dorsal telencephalic cell types and gene expression patterns are lost in homozygous XtJ mutants, and features of ventral telencephalic identity develop ectopically in the dorsal telencephalon. This partial ventralization of the dorsal telencephalon does not appear to be induced by an expansion of Sonic hedgehog expression in the telencephalon, but may be due to a loss ofBmp and Wnt gene expression in a putative dorsal telencephalic signaling center, the cortical hem. Our findings suggest that in dorsal telencephalon Gli3 is needed to repress ventral telencephalic identity
The Phosphoprotein Protein PEA-15 Inhibits Fas- but Increases TNF-R1-Mediated Caspase-8 Activity and Apoptosis

AbstractWe have characterized a phosphoprotein protein with a death effector domain that has a novel bifunctional role in programmed cell death. The 15-kDa phosphoprotein enriched in astrocytes (PEA-15) inhibits Fas-mediated apoptosis and increases tumor necrosis factor receptor-1 (TNF-R1)-mediated apoptosis in the same cell type in a ligand-dependent manner. Phosphorylation appears to play a role in its differential effects, since point mutations at one or both phosphorylation consensus sites within PEA-15 destroy its effect on Fas-mediated, but not TNF-R1-mediated, apoptosis. Furthermore, the differential effect is evident at the level of caspase-8 activity which is inhibited via Fas activation, but increased via TNF-R1 activation upon PEA-15 expression. These results show that PEA-15 provides a potential mechanism during development for distinguishing between diverse extracellular death-inducing signals that culminate either in apoptosis or in survival
Gliogenesis Depends on glide/gcm through Asymmetric Division of Neuroglioblasts

AbstractSome neurons and glial cells originate from neuroblasts and glioblasts, stem cells that delaminate from the ectoderm of developing fly embryos. A second class of glial cells and neurons differentiates from multipotent precursors, the neuroglioblasts. The differentiation of both glial cell types depends on glial cell deficient/glial cell missing (glide/gcm). Although it has been shown that this transcription factor promotes gliogenesis at the expense of neurogenesis, the cellular mechanisms underlying this fate choice are poorly understood. Using loss and gain of function glide/gcm mutations here we show that the cell fate choice takes place in the neuroglioblast, which divides and produces a glioblast and a neuroblast. Such choice requires the asymmetric distribution of glide/gcm RNA, which accumulates preferentially on one side of the neuroglioblast and is inherited by one cell, the presumptive glioblast. Interestingly, glial cells can differentiate from cells that delaminate as neuroglioblasts or they can arise from cells that start expressing glide/gcm several hours after delamination of a neuroblast. Altogether, these findings identify a novel type of asymmetric cell division and disclose the lineage relationships between glia and neurons. They also reveal the mode of action of the glide/gcm promoting factor
Plasticity of Axial Identity among Somites: Cranial Somites Can Generate Vertebrae without Expressing Hox Genes Appropriate to the Trunk

AbstractClassic studies have shown that the presomitic mesoderm is already committed to a specific morphological fate, for example, the ability to generate a rib. Hox gene expression in the paraxial mesoderm has also been shown to be fixed early and not susceptible to modulation by an ectopic environment. This is in contrast to the plasticity of Hox expression in neuroectodermal derivatives. We reexamine here the potential of somites for morphological plasticity by transplanting the cranial (occipital) somites 1–4, that normally produce small contributions to the skull, to the trunk of avian embryos. Surprisingly, the transposed cranial somites are able to form reasonably normal vertebral anlage. In addition, the cranial somitic mesoderm produces intervertebral disks, structures not normally found in the skull. These somites are however unable to generate some elements of the vertebrae, such as the costal process. In contrast to the morphogenetic plasticity of the occipital somites, their characteristic inability to support survival of dorsal root ganglia was not significantly modified by posterior transplantation. Dorsal root ganglia initially developed and then degenerated with the same morphological stages as normally observed. In striking contrast to the plasticity of morphology, we found that all four members of the of the fourth paralogous group of Hox genes that are expressed endogenously at the level of the graft are not upregulated in the caudad-transposed cranial mesoderm. It therefore appears that genes other than those of the Hox family normally expressed at this axial level control the position-specific morphogenesis of ectopic vertebrae formed from cranial somites. In evolutionary terms, the present results imply that occipital somites that were incorporated into the “New Head” retain the ability to develop according to their original morphogenetic fate, into vertebrae
The Roles of Changes in NADPH and pH during Fertilization and Artificial Activation of the Sea Urchin Egg

AbstractIncubating unfertilized sea urchin eggs in weak bases activates nuclear centering, DNA synthesis, and chromosome cycles. These effects were initially attributed to raising the intracellular pH (pHi), but later experiments indicated that these weak bases also lead to increases in reduced pyridine nucleotides. These findings raised the question whether the activation of the nucleus was due to increased pHi or to increased NAD(P)H or possibly other effects. This report attempts to clarify how ammonia activates eggs by independently altering NADPH and pHi. To increase the pHi, unfertilized eggs were injected with zwitterionic buffers. This stimulated pronuclear centering, DNA synthesis, and nuclear envelope breakdown; there appeared to be a threshold corresponding to the fertilized pHi. However, like incubation in ammonia, injection of base also increased NAD(P)H. The NAD(P)H rise caused by directly raising the pHi occurred in the presence of intracellular calcium chelators, indicating that calcium is not required. Increasing NAD(P)H alone did not activate nuclear centering, DNA synthesis, or nuclear envelope breakdown. Although these experiments cannot eliminate a role for the NADPH increase in initiating events leading to nuclear centering and entry into mitosis, they provide additional and strong evidence that increasing the pHi may be a primary signal
Cusp Patterning Defect in Tabby Mouse Teeth and Its Partial Rescue by FGF

AbstractTabby is a mouse mutant characterized by deficient development of the ectodermal organs: teeth, hair, and a subset of glands. Ectodysplasin, the protein encoded by the Tabby gene, was recently identified as a novel TNF-like transmembrane protein but little is known about its function. We have examined the Tabby tooth phenotype in detail by analysis of the adult and embryonic teeth. Tabby first molars had an obvious defect in cusp patterning as the number of cusps was reduced and the buccal and lingual cusps were joined. The disturbance in development was first visible morphologically in the bud stage molar. The primary enamel knot in a cap stage Tabby tooth expressed all enamel knot markers analyzed but was smaller than wild type and the first pair of developing secondary enamel knots was fused. We propose that the Tabby tooth phenotype is due to growth retardation during early stages of development which leads to reduced signaling from the primary enamel knot, followed by deficient growth of the dental epithelium and lack of formation of the last developing secondary enamel knots. The ectodysplasin transcripts were expressed in the outer enamel epithelium and dental lamina. When cultured in vitro Tabby bud/cap stage molars formed fewer cusps than wild-type controls. This phenotype was not rescued by exogenously added EGF despite the previously proposed link between Tabby and EGF. Instead FGF-10 partially restored morphogenesis and stimulated the development of additional tooth cusps in cultured Tabby molars
FGF Signaling and the Anterior Neural Induction in Xenopus

AbstractWe previously showed that FGF was capable of inducing Xenopus gastrula ectoderm cells in culture to express position-specific neural markers along the anteroposterior axis in a dose-dependent manner. However, conflicting results have been obtained concerning involvement of FGF signaling in the anterior neural induction in vivo using the same dominant-negative construct of Xenopus FGF receptor type-1 (ΔXFGFR-1 or XFD). We explored this issue by employing a similar construct of receptor type-4a (XFGFR-4a) in addition, since expression of XFGFR-4a was seen to peak between gastrula and neurula stages, when the neural induction and patterning take place, whereas expression of XFGFR-1 had not a distinct peak during that period. Further, these two FGFRs are most distantly related in amino acid sequence in the Xenopus FGFR family. When we injected mRNA of a dominant-negative version of XFGFR-4a (ΔXFGFR-4a) into eight animal pole blastomeres at 32-cell stage, anterior defects including loss of normal structure in telencephalon and eye regions became prominent as examined morphologically or by in situ hybridization. Overexpression of ΔXFGFR-1 appeared far less effective than that of ΔXFGFR-4a. Requirement of FGF signaling in ectoderm for anterior neural development was further confirmed in culture: when ectoderm cells that were overexpressing ΔXFGFR-4a were cocultured with intact organizer cells from either early or late gastrula embryos, expression of anterior and posterior neural markers was inhibited, respectively. We also showed that autonomous neuralization of the anterior-type observed in ectoderm cells that were subjected to prolonged dissociation was strongly suppressed by ΔXFGFR-4a, but not as much by ΔXFGFR-1. It is thus indicated that FGF signaling in ectoderm, mainly through XFGFR-4, is required for the anterior neural induction by organizer. We may reconcile our data to the current “neural default model,” which features the central roles of BMP4 signaling in ectoderm and BMP4 antagonists from organizer, simply postulating that the neural default pathway in ectoderm includes constitutive FGF signaling step
The Dynamic Expression Pattern of frzb-1 Suggests Multiple Roles in Chick Development

AbstractThe Wnt family of secreted proteins has been shown to have multiple roles in embryonic development. Wnt signals are thought to be propagated by binding to the cysteine-rich extracellular domain (CRD) of Frizzled, a seven-transmembrane-domain cell surface receptor. Secreted Frizzled-related proteins (generally denoted Frzb or Sfrp) possess a domain with a high degree of sequence identity and structural similarity with the CRD of Frizzled. Current data indicate that the cysteine-rich domain of secreted Frzb proteins can bind Wnt proteins, suggesting the possibility that Frzbs compete with membrane-bound Frizzled for Wnt binding and consequently act as competitive inhibitors of Wnt signaling. In order to gain a better understanding of the potential roles of Frzb-1 in chick development, we utilized the polymerase chain reaction to isolate a partial cDNA of the chick orthologue of frzb-1, cfrzb-1, and compared its expression pattern to that of Wnt-1, Wnt-3a, Wnt-5a, Wnt-7a, and Wnt-8c. Whole-mount in situ hybridizations have revealed three major phases of expression for cfrzb-1 in the developing chick. The earliest expression of cfrzb-1 is in cells fated to become neural ectoderm in streak-stage embryos. Expression of cfrzb-1 in the neural ectoderm continues up through stage 8. After stage 8, cfrzb-1 expression is gradually attenuated in the closing neural tube of the trunk and is concomitantly up-regulated in neural crest cells. Finally, cfrzb-1 appears in the condensing mesenchyme of the bones in both the limb and the trunk in stage 25+ embryos. Comparative analysis of the cfrzb-1 and the Wnt gene expression patterns suggests possible interactions between cFrzb-1 and all of the Wnt family members examined
Expression of the Cytoplasmic Domain of E-cadherin Induces Precocious Mammary Epithelial Alveolar Formation and Affects Cell Polarity and Cell–Matrix Integrity

AbstractCadherins are cell adhesion molecules involved in cell–cell adhesion, signalling, and cellular proliferation and differentiation. E-cadherin is required for the formation of epithelium in vivo. We investigated the contribution of the cytoplasmic domain of E-cadherin to adhesion, signalling, and differentiation during murine mammary gland development, by in vivo expression of a gene encoding a truncated form of E-cadherin lacking the extracellular domain. The expression of this gene in mammary epithelial cells during pregnancy induced precocious lobular epithelial morphogenesis associated with morphological differentiation and the early synthesis of various molecules (advanced milk fat globule appearance and milk protein production). After delivery, when a fully differentiated and secretory epithelium is required for lactation, the cytoplasmic domain of E-cadherin had a dominant-negative effect on cell–cell adhesion and affected the structure and function of the epithelium. This also led to the partial loss of epithelial polarisation and changes in the basement membrane, both important in malignancy. Thus, the cytoplasmic domain of E-cadherin induces epithelial morphogenesis, but also alters the cohesiveness of the fully differentiated epithelium
Activation of Stat3 by Cytokine Receptor gp130 Ventralizes Xenopus Embryos Independent of BMP-4

AbstractStat3 is one of the main signaling components of cytokine receptors, including gp130. Here we show that activation of cytokine receptor gp130 resulted in a dramatic ventralization of Xenopus embryos and that the ventralization correlated well with Stat3 activation potential of the receptor. This finding led to identification of Xenopus Stat3 (Xstat3), which showed a 95% homology to its murine and human counterparts, at the amino acid level, and was expressed from the one-cell stage throughout development. The mechanism of gp130/XStat3-mediated ventralization proved to be independent of BMP-4. gp130/Xstat3 stimulation inhibited Smad2-induced ectopic axis formation in embryos and Smad2-dependent luciferase activity. A dominant-negative Stat3, in contrast, dorsalized Xenopus embryos, resulting in ectopic axis formation. We propose that Stat3-mediated signaling has the capacity to modify dorsoventral patterning in the early development of Xenopus