pinecone/core-2020-05-10-deduplication huggingface dataset:
A heart segmental defect in the anterior-posterior axis of a transgenic mutant mouse

A recessive lethal insertional mutation on chromosome 13 has been identified in a transgenic mouse line that displays a segmental form of cardiac defect along the anterior-posterior axis in all homozygous mice identified. The most anterior segment (future conus and right ventricle) of the single heart tube fails to develop normally and the endocardial cushions in both the conus and the atrioventricular regions are missing. Analysis of the β-galactosidase reporter portion of the transgene during embryonic development shows a segmental expression of activity primarily in the defective outlet of the primitive heart. In addition to expression in the heart tube, hemizygous embryos show transgene expression in the chondrogenic regions of first and second branchial arches, the appendicular skeleton, and the dermal papillae of the vibrissae. The restricted pattern of β-galactosidase expression in the heart can be disrupted with retinoic acid exposure and extended posteriorly along the anterior-posterior axis in hemizygous mice. Although cushion mesenchyme fail to form in the homozygous mutant, the myocardial and endothelial cells explanted from the mutant atrioventricular, but not the conus, are capable of forming mesenchyme in vitro. Mice trisomic for chromosome 13 have also been shown to display segmental anomalies associated with the anterior primitive outlet segments of the heart. Our data show that this insertional mutation identifies a new gene locus, hdf (heart defect), on mouse chromosome 13 that may be required for mechanisms that initially establish and/or maintain continued development of the anterior limb of the developing heart. The hdf mouse mutation also provides a new model system to evaluate the molecular requirements of normal endocardial cushion formation and the segmental interactions that form the adult heart
Cell-Junctional and Cytoskeletal Organization in Mouse Blastocysts Lacking E-Cadherin

AbstractTrophectoderm epithelium formation, the first visible differentiation process during mouse embryonic development, is affected in embryos lacking the cell adhesion molecule E-cadherin. Here we analyze the developmental potential of such E-cadherin-negative embryos, focusing on the organization of cell junctions and the cytoskeleton. To do this we used antibodies directed against α-, β-, or γ-(plakoglobin)-catenin and junctional and cytoskeletal proteins including ZO-1 and occludin (tight junctions), desmoglein1 (desmosomes), connexin43 (gap junctions), and EndoA (cytokeratin intermediate filaments). Membrane localization of α- and β-catenin, and ZO-1, as well as cortical actin filament organization were abnormal in E-cadherin-negative embryos, and the expression levels of α- and β-catenin were dramatically reduced, all suggesting a regulatory role for E-cadherin in forming the cadherin–catenin complex. In contrast, the membrane localization of plakoglobin, occludin, desmoglein1, connexin43, and cytokeratin filaments appeared unaltered. The unusual morphogenesis in E-cadherin-negative embryos apparently reflects defects in the molecular architecture of a supermolecular assembly involving zonulae adherens, tight junctions, and cortical actin filament organization, although the individual structures still appeared normal in electron microscopical analysis
Regulation ofparaxisExpression and Somite Formation by Ectoderm- and Neural Tube-Derived Signals

AbstractDuring vertebrate embryogenesis, the paraxial mesoderm becomes segmented into somites, which form as paired epithelial spheres with a periodicity that reflects the segmental organization of the embryo. As a somite matures, the ventral region gives rise to a mesenchymal cell population, the sclerotome, that forms the axial skeleton. The dorsal region of the somite remains epithelial and is called dermomyotome. The dermomyotome gives rise to the trunk and limb muscle and to the dermis of the back. Epaxial and hypaxial muscle precursors can be attributed to distinct somitic compartments which are laid down prior to overt somite differentiation. Inductive signals from the neural tube, notochord, and overlying ectoderm have been shown to be required for patterning of the somites into these different compartments. Paraxis is a basic helix–loop–helix transcription factor expressed in the unsegmented paraxial mesoderm and throughout epithelial somites before becoming restricted to epithelial cells of the dermomyotome. To determine whether paraxis might be a target for inductive signals that influence somite patterning, we examined the influence of axial structures and surface ectoderm on paraxis expression by performing microsurgical operations on chick embryos. These studies revealed two distinct phases of paraxis expression, an early phase in the paraxial mesoderm that is dependent on signals from the ectoderm and independent of the neural tube, and a later phase that is supported by redundant signals from the ectoderm and neural tube. Under experimental conditions in which paraxis failed to be expressed, cells from the paraxial mesoderm failed to epithelialize and somites were not formed. We also performed an RT-PCR analysis of combined tissue explantsin vitroand confirmed that surface ectoderm is sufficient to induce paraxis expression in segmental plate mesoderm. These results demonstrate that somite formation requires signals from adjacent cell types and that theparaxisgene is a target for the signal transduction pathways that regulate somitogenesis
Genetic Relationships between the MutationsspadeandSternopleuraland thewinglessGene inDrosophilaDevelopment

AbstractInDrosophila melanogaster,there are cases in which gene products contributing to the same developmental event may derive from closely adjacent transcription units and may even sharecis-regulatory sequences. Correct recognition of such genomic organization is central to an understanding of developmental mechanisms. The adult phenotypes of combinations between the mutationsspade, Sternopleural,andwinglesssuggest that they are lesions in functionally related genes within the same chromosomal region.winglessmutations fail to complement the recessive mutationspade.Thespademutation, as previously shown, behaves as a lesion in a regulatory site ofwingless,sited 5′ to the transcription unit, and is concerned with particular postembryonic functions ofwingless.While showingwingless-like phenotypes in combination withSternopleural,even lethal alleles ofwinglesscomplement the recessive lethality ofSternopleuralalleles. Mutations inSternopleuralincrease the severity ofwinglessphenotypes in manywingless-dependent processes during postembryonic development, and this interaction can occur when the only functional copies ofSporwgare located in either opposing chromosomes or the same chromosome. This is inconsistent with previous attempts to defineSpas a regulatory allele ofwgand explain the phenotypes that result from combinations ofSpandwgby means of transvection. We have analyzed a new EMS-induced allele ofSternopleuralthat is more severe than the original allele, which also argues forSpbeing a separate, mutable genetic locus rather than a regulatory allele ofwg.Finally, we have a revertant ofSternopleural(SpRv1) that behaves as a genetic null allele ofwg,but causes ventral-to-dorsal transformations in combination withwgP,which is not observed in combinations ofwgnull alleles withwgP.BecausewgPis the result of an inversion and because inversions inhibit transvection, the increased severity observed inSpRv1/wgPin comparison towgnull/SpRv1animals cannot be explained by an absence of transvection. Therefore, the twoSternopleuralmutations most reasonably define an independent gene located 3′ to thewinglessgene and having strong functional synergism with it
Neural Crest Potential for Tooth Development in a Urodele Amphibian: Developmental and Evolutionary Significance

AbstractTooth development in urodele amphibians occurs from a restricted region of anterior cranial neural crest. Anin vitroculture system was used to test the odontogenic potential of more caudal regions of neural crest, including an “intermediate region” of neural folds which has never previously been tested for either fate or potential. Explants of different axial levels of neural crest with stomodaeal ectoderm and endoderm demonstrated that odontogenic potential extends not only further caudally than the axial level fated to produce teeth, but also beyond that with potential to produce cartilage. Our results show that chondrogenic potential is found only within the most rostral portion of the intermediate region, but that odontogenic potential extends to its most caudal limit. This separation of skeletogenic cell lineages in the neural crest necessitates a reevaluation of the designations of “cranial” and “trunk” and a reconsideration of the evolutionary implications of developmentally distinct crest-derived mesenchyme populations. The proposal that odontogenic potential extends into the trunk neural crest may be explained as conserved from a phylogenetically older, more extensive skeletogenic ability which produced the exoskeleton of more basal vertebrates
Wild-Type Myoblasts Rescue the Ability of Myogenin-Null Myoblasts to Fusein Vivo

AbstractSkeletal muscle is formed via a complex series of events during embryogenesis. These events include commitment of mesodermal precursor cells, cell migration, cell–cell recognition, fusion of myoblasts, activation of structural genes, and maturation. In mice lacking the bHLH transcription factor myogenin, myoblasts are specified and positioned correctly, but few fuse to form multinucleated fibers. This indicates that myogenin is critical for the fusion process and subsequent differentiation events of myogenesis. To further define the nature of the myogenic defects in myogenin-null mice, we investigated whether myogenin-null myoblasts are capable of fusing with wild-type myoblastsin vivousing chimeric mice containing mixtures of myogenin-null and wild-type cells. Chimeric embryos demonstrated that myogenin-null myoblasts readily fused in the presence of wild-type myoblasts. However, chimeric myofibers did not express wild-type levels of muscle-specific gene products, and myofibers with a high percentage of mutant nuclei appeared abnormal, suggesting that the wild-type nuclei could not fully rescue mutant nuclei in the myofibers. These data demonstrate that myoblast fusion can be uncoupled from complete myogenic differentiation and that myogenin regulates a specific subset of genes with diverse function. Thus, myogenin appears to control not only transcription of muscle structural genes but also the extracellular environment in which myoblast fusion takes place. We propose that myogenin regulates the expression of one or more extracellular or cell surface proteins required to initiate the muscle differentiation program
Xwnt-8 and lithium can act upon either dorsal mesodermal or neurectodermal cells to cause a loss of forebrain in Xenopus embryos

When Xenopus gastrulae are made to misexpress Xwnt-8, or are exposed to lithium ions, they develop with a loss of anterior structures. In the current study, we have characterized the neural defects produced by either Xwnt-8 or lithium and have examined potential cellular mechanisms underlying this anterior truncation. We find that the primary defect in embryos exposed to lithium at successively earlier stages during gastrulation is a progressive rostral to caudal deletion of the forebrain, while hindbrain and spinal regions of the CNS remain intact. Misexpression of Xwnt-8 during gastrulation produces an identical loss of forebrain. Our results demonstrate that lithium and Wnts can act upon either prospective neural ectodermal cells, or upon dorsal mesodermal cells, to cause a loss of anterior pattern. Specifically, ectodermal cells isolated from lithium- or Wnt-exposed embryos are unable to form anterior neural tissue in response to inductive signals from normal dorsal mesoderm. In addition, although dorsal mesodermal cells from lithium- or Wnt-exposed embryos are specified properly, and produce normal levels of the anterior neural inducing molecules noggin and chordin, they show a greatly reduced capacity to induce anterior neural tissue in conjugated ectoderm. Taken together, our results are consistent with a model in which Wnt- or lithium-mediated signals can induce either mesodermal or ectodermal cells to produce a dominant posteriorizing morphogen which respecifies anterior neural tissue as posterior
Developmental Expression of BPAG1-n: Insights into the Spastic Ataxia and Gross Neurologic Degeneration inDystonia MusculorumMice

AbstractAblation of theBPAG1gene results in thedystonia musculorummouse, exhibiting rapid spinal nerve degeneration, dystonic movements, and severe ataxia. By defining the developmental and tissue-specific expression of the neuronal form of BPAG1 (BPAG1-n) and by comparing the corresponding pathology in BPAG1 null mice, we seek here to understand how absence of BPAG1 results in this devastating phenotype in mice and in potentially related human neurological disorders. Throughout normal development, BPAG1-n was expressed in a variety of sensory and autonomic neuronal structures, but was absent or reduced in areas such as basal ganglia that are often affected in dystonias and ataxias. Interestingly, BPAG1-n was also expressed broadly in embryonic motor neurons, but expression declined dramatically after birth. Despite these complex developmental patterns, BPAG1−/− pathology was restricted largely to postnatal development. Moreover, gross neuronal degeneration was restricted to only a few regions where BPAG1-n was found, including dorsal root ganglion neurons and a small subset of motor neurons. Most notably, while skeletal muscle was normal, appearance of severe dystonic ataxia correlated with postnatal degeneration of muscle spindles. Collectively, our findings suggest a mechanism for the BPAG1 null phenotype and indicate that different neurons respond differently to the absence of BPAG1-n, a cytoskeletal linker protein
N-Cadherin–Catenin Interaction: Necessary Component of Cardiac Cell Compartmentalization during Early Vertebrate Heart Development

AbstractDuring early heart development the expression pattern of N-cadherin, a calcium-dependent cell adhesion molecule, suggests its involvement in morphoregulation and the stabilization of cardiomyocyte differentiation. N-cadherin's adhesive activity is dependent upon its interaction with the intracellular catenins. An association with α-catenin and β-catenin also is believed to be involved in cell signaling. This study details the expression patterns of α-catenin, β-catenin, and γ-catenin, during definition of the cardiac cell population as distinct compartments in the anterior regions of the chick embryo between stages 5 and 9. The restriction of N-cadherin/catenin localization at stage 5+ from a uniform patternin vivo,to specific cell clusters that demarcate areas where mesoderm separation is initiated, suggests that the N-cadherin/catenin complex is involved in boundary formation and in the subsequent cell sorting. The latter two processes lead to the specification and formation of the somatic and cardiac splanchnic mesoderm. N-cadherin colocalized with α- and β-catenin at the cell membrane before and during the time that its expression becomes restricted to the lateral mesoderm and continues cephalocaudad into stage 8. These proteins continue to colocalize in the myocardium of the tubular heart. Plakoglobin is not expressed in this region during stages 6–8, but is detected in the myocardium later at stage 13. The observedin vivoexpression patterns of α-catenin, β-catenin, and plakoglobin suggest that these proteins are directly linked with the developmental regulation of cell junctions, as cardiac cells become stably committed and phenotypically differentiated to eventually form a mature myocardium. The localization of N-CAM also was analyzed during these stages to determine whether the N-cadherin–catenin localization was unique or whether other cell adhesion molecules were expressed similarly. The results indicate that the unique pattern of N-cadherin expression is not shared with N-CAM. We also show that perturbation of N-cadherin using a function perturbing N-cadherin antibody (NCD-2) inhibits normal early heart development and myogenesis in a cephalocaudad, stage-dependent manner. We propose a model whereby myocardial cell compartmentalization also defines the endocardial population. The presence of β-catenin suggests that a similar signaling pathway involvingWnt(wingless)-mediated events may function in myocardial cell compartmentalization during early vertebrate heart development, as inDrosophilacontractile vessel development
Inhibition of Morphogenetic Movement duringXenopusGastrulation by Injected Sulfatase: Implications for Anteroposterior and Dorsoventral Axis Formation

AbstractIn order to explore the role of morphogenetic movement in the establishment of anteroposterior and dorsoventral axes, we sought to identify novelin vivoinhibitors of gastrulation movements inXenopus laevis.Injection of hydrolytic sulfatase into the blastocoels of gastrula stage embryos resulted in severe anteroposterior truncation, without a corresponding truncation of the dorsoventral axis. Confocal microscopy of whole embryos revealed that gastrulation movements are severely disrupted by sulfatase; in addition, sulfatase dramatically inhibited chordomesodermal cell elongation and convergent extension movements in planar dorsal marginal zone explants. The phenotype of anteroposterior reduction elicited by sulfatase is distinctly different from commonly generated dorsoanterior phenotypes (e.g., ultraviolet irradiation of the vegetal cortex prior to cortical rotation or suramin injection), and the two varieties of phenotype appear to result from inhibition of distinct, separable components of the axis-generating machinery
XATH-1,a Vertebrate Homolog ofDrosophila atonal,Induces Neuronal Differentiation within Ectodermal Progenitors

AbstractXATH-1,a basic/helix-loop-helix transcription factor and a homolog ofDrosophila atonaland mammalianMATH-1,is expressed specifically in the dorsal hindbrain duringXenopusneural development. In order to investigate the role ofXATH-1in the neuronal differentiation process, we have examined the effects ofXATH-1overexpression duringXenopusdevelopment.XATH-1induces the expression of neuronal differentiation markers, such asN-tubulin,within the neural plate as well as within nonneural ectodermal progenitor populations, resulting in the appearance of process-bearing neurons within the epidermis. The related basic/helix-loop-helix genesneurogenin-related-1andneuroDare not induced in response toXATH-1overexpression within the embryo, suggesting thatXATH-1may activate an alternate pathway of neuronal differentiation. In further contrast toneurogenin-related-1andneuroD,high-level expression of general neural markers expressed earlier in development, such asN-CAM,is not induced byXATH-1overexpression. Competent ectodermal progenitors therefore respond to ectopicXATH-1expression by initiating a distinct program of neuronal differentiation
Lens Induction by Pax-6 inXenopus laevis

AbstractDespite extensive study following the pioneering work of Spemann on lens development (Spemann, H. (1901)Verh. Anat. Ges.15, 61–79) and the subsequent establishment of the concept of embryonic induction, the molecular mechanism of vertebrate lens induction remains largely unknown. Here we report that inXenopusexpression of Pax-6 results in lens formation in a cell autonomous manner. In animal cap experiments, Pax-6 induced expression of the lens-specific marker βB1-crystallin without inducing the general neural marker NCAM. Ectopic Pax-6 expression also resulted in the formation of ectopic lenses in whole embryos as well as in animal cap explants indicating that in vertebrates, as well asDrosophila(Halder, G., Callaerts, P., and Gehring, W.J. (1995)Science267, 1788–1792), Pax-6 can direct the development of major components of the eye. Interestingly, ectopic lenses formed in whole embryos without association with neural tissue. Treatments giving rise to anterior neural tissue in animal cap explants resulted in the expression of both βB1-crystallin and Pax-6. Given the ability of Pax-6 to direct lens formation, we propose that the establishment of Pax-6 expression in the presumptive lens ectoderm during normal development is likely to be a critical response of lens-competent ectoderm to early lens inducers
Identification of a male meiosis-specific gene, Tcte2, which is differentially spliced in species that form sterile hybrids with laboratory mice and deleted in t chromosomes showing meiotic drive

Tcte2 (t complex testes expressed 2) is a male meiosis-specific gene that maps to band 3.3 of mouse chromosome 17. Two distinct male fertility defects, hybrid sterility and transmission ratio distortion, have previously been mapped to this region. Hybrid sterility arises in crosses between different mouse species and the F1 generation males have defects in the first meiotic division and are sterile. Transmission ratio distortion is shown by males heterozygous for the t haplotype form of chromosome 17 and is a type of meiotic drive in which male gametes function unequally at fertilization. The Tcte2 gene expresses a coding mRNA and a number of putative non-ORF transcripts in meiosis I. A deletion of the 5′ part of the locus abolishes Tcte2 expression on the t haplotype form of chromosome 17. Additionally, the series of putative non-ORF RNAs at the Tcte2 locus are differentially spliced in species that show hybrid sterility when crossed to laboratory mice. The identification of polymorphisms in t haplotypes and in different mouse species allows alleles of Tcte2 to be proposed as candidates for loci which contribute to both meiotic drive and hybrid sterility phenotypes. While theoretical considerations have previously been used to propose that speciation and meiotic drive involve alleles of the same genes, Tcte2 is the first cloned candidate gene to support this link at a molecular level
Temporal and Spatial Control of Murine GATA-3 Transcription by Promoter-Proximal Regulatory Elements

AbstractGATA-3 is expressed in a temporally dynamic manner and fulfills vital functions during vertebrate fetal development. Homozygous mGATA-3 mutant embryos die at midgestation, thus complicating the analysis of its contribution to the development of specific cell fates in the many tissues where it is expressed during embryogenesis. We show here that the elements controlling GATA-3 regulation can be precisely refined, using transgenic mice, to discretecis-acting domains: within 6 kb surrounding the transcriptional initiation site, separate sequences were found to control the expression of mGATA-3 in early muscle masses, in a subset of PNS neurons, in the genital tubercle, and in the branchial arches. The branchial arch regulatory element is particularly robust and was refined to a discrete enhancer sequence lying between nt −2832 and −2462 from the transcription initiation site. The enhancer contains potential binding sites for many well-characterized transcription factors, suggesting that mGATA-3 transcriptional activity may be regulated by these proteins (or related family members) in the mesenchyme of the arches that contribute to formation of the jaw. These studies show that discrete regulatory elements required for the elaboration of complex developmental programs can be individually localized, suggesting that the developmentally transient expression of individual transcription factors collaboratively contributes to the temporal and spatial pattern of cellular differentiation leading to the formation of adult anatomy