pinecone/core-2020-05-10-deduplication huggingface dataset:
Trophoblast-Specific Expression and Function of the Integrin α7 Subunit in the Peri-implantation Mouse Embryo

AbstractFor implantation and placentation to occur, mouse embryo trophoblast cells must penetrate the uterine stroma to make contact with maternal blood vessels. A major component of the uterine epithelial basement membrane and underlying stromal matrix with which they interact is the extracellular matrix protein laminin. We have identified integrin α7β1 as a major receptor for trophoblast–laminin interactions during implantation and yolk sac placenta formation. It is first expressed by trophectoderm cells of the late blastocyst and by all trophectoderm descendants in the early postimplantation embryo through E8.5, then disappears except in cells at the interface between the allantois and the ectoplacental plate. Integrin α7 expression is a general characteristic of the early differentiation stages of rodent trophoblast, given that two different cultured trophoblast cell lines also express this integrin. Trophoblast cells interact with at least three different laminin isoforms (laminins 1, 2/4, and 10/11) in the blastocyst and in the uterus at the time of implantation. Outgrowth assays using function-blocking antibodies show that α7β1 is the major trophoblast receptor for laminin 1 and a functional receptor for laminins 2/4 and 10/11. When trophoblast cells are cultured on substrates of these three laminins, they attach and spread on all three, but show decreased proliferation on laminin 1. These results show that the α7β1 integrin is expressed by trophoblast cells and acts as receptor for several isoforms of laminin during implantation. These interactions are not only important for trophoblast adhesion and spreading but may also play a role in regulating trophectoderm proliferation and differentiation
Dorsal Pancreas Agenesis in N-Cadherin- Deficient Mice

AbstractMembers of the cadherin family of cell adhesion molecules are thought to be crucial regulators of tissue patterning and organogenesis. During pancreatic ontogeny N-cadherin is initially expressed in the pancreatic mesenchyme and later in pancreatic endoderm. Analysis of N-cadherin-deficient mice revealed that these mice suffer from selective agenesis of the dorsal pancreas. Further analysis demonstrated that the mechanism for the lack of a dorsal pancreas involves an essential function of N-cadherin as a survival factor in the dorsal pancreatic mesenchyme
The Nrarp Gene Encodes an Ankyrin-Repeat Protein That Is Transcriptionally Regulated by the Notch Signaling Pathway

AbstractWe have identified a gene encoding a novel protein that is transcriptionally regulated by the Notch signaling pathway in mammals. This gene, named Nrarp (for Notch-regulated ankyrin-repeat protein), encodes a 114 amino acid protein that has a unique amino-terminus and a carboxy-terminal domain containing two ankyrin-repeat motifs. A Xenopus homolog of the Nrarp gene was previously identified in a large-scale in situ hybridization screen of randomly isolated cDNA clones. We demonstrate that in T-cell and myoblast cell lines expression of the Nrarp gene is induced by the intracellular domain of the Notch1 protein, and that this induction is mediated by a CBF1/Su(H)/Lag-1 (CSL)-dependent pathway. During mouse embryogenesis, the Nrarp gene is expressed in several tissues in which cellular differentiation is regulated by the Notch signaling pathway. Expression of the Nrarp gene is downregulated in Notch1 null mutant mouse embryos, indicating that expression of the Nrarp gene is regulated by the Notch pathway in vivo. Thus, Nrarp transcript levels are regulated by the level of Notch1 signaling in both cultured cell lines and mouse embryos. During somitogenesis, the Nrarp gene is expressed in a pattern that suggests that Nrarp expression may play a role in the formation of somites, and Nrarp expression in the paraxial mesoderm is altered in several Notch pathway mutants that exhibit defects in somite formation. These observations demonstrate that the Nrarp gene is an evolutionarily conserved transcriptional target of the Notch signaling pathway
The Outflow Tract of the Heart Is Recruited from a Novel Heart-Forming Field

AbstractAs classically described, the precardiac mesoderm of the paired heart-forming fields migrate and fuse anteriomedially in the ventral midline to form the first segment of the straight heart tube. This segment ultimately forms the right trabeculated ventricle. Additional segments are added to the caudal end of the first in a sequential fashion from the posteriolateral heart-forming field mesoderm. In this study we report that the final major heart segment, which forms the cardiac outflow tract, does not follow this pattern of embryonic development. The cardiac outlet, consisting of the conus and truncus, does not derive from the paired heart-forming fields, but originates separately from a previously unrecognized source of mesoderm located anterior to the initial primitive heart tube segment. Fate-mapping results show that cells labeled in the mesoderm surrounding the aortic sac and anterior to the primitive right ventricle are incorporated into both the conus and the truncus. Conversely, if cells are labeled in the existing right ventricle no incorporation into the cardiac outlet is observed. Tissue explants microdissected from this anterior mesoderm region are capable of forming beating cardiac muscle in vitro when cocultured with explants of the primitive right ventricle. These findings establish the presence of another heart-forming field. This anterior heart-forming field (AHF) consists of mesoderm surrounding the aortic sac immediately anterior to the existing heart tube. This new concept of the heart outlet's embryonic origin provides a new basis for explaining a variety of gene-expression patterns and cardiac defects described in both transgenic animals and human congenital heart disease
FGFR3 Expression during Development and Regeneration of the Chick Inner Ear Sensory Epithelia

AbstractSeveral studies suggest fibroblast growth factor receptor 3 (FGFR3) plays a role in the development of the auditory epithelium in mammals. We undertook a study of FGFR3 in the developing and mature chicken inner ear and during regeneration of this epithelium to determine whether FGFR3 shows a similar pattern of expression in birds. FGFR3 mRNA is highly expressed in most support cells in the mature chick basilar papilla but not in vestibular organs of the chick. The gene is expressed early in the development of the basilar papilla. Gentamicin treatment sufficient to destroy hair cells in the basilar papilla causes a rapid, transient downregulation of FGFR3 mRNA in the region of damage. In the initial stages of hair cell regeneration, the support cells that reenter the mitotic cycle in the basilar papilla do not express detectable levels of FGFR3 mRNA. However, once the hair cells have regenerated in this region, the levels of FGFR3 mRNA and protein expression rapidly return to approximate those in the undamaged epithelium. These results indicate that FGFR3 expression changes after drug-induced hair cell damage to the basilar papilla in an opposite way to that found in the mammalian cochlea and may be involved in regulating the proliferation of support cells
Estrogen Receptor-α Knockout Mice Exhibit Resistance to the Developmental Effects of Neonatal Diethylstilbestrol Exposure on the Female Reproductive Tract

AbstractData indicate that estrogen-dependent and -independent pathways are involved in the teratogenic/carcinogenic syndrome that follows developmental exposure to 17β-estradiol or diethylstilbestrol (DES), a synthetic estrogen. However, the exact role and extent to which each pathway contributes to the resulting pathology remain unknown. We employed the αERKO mouse, which lacks estrogen receptor-α (ERα), to discern the role of ERα and estrogen signaling in mediating the effects of neonatal DES exposure. The αERKO provides the potential to expose DES actions mediated by the second known ER, ERβ, and those that are ER-independent. Wild-type and αERKO females were treated with vehicle or DES (2 μg/pup/day for Days 1–5) and terminated after 5 days and 2, 4, 8, 12, and 20 months for biochemical and histomorphological analyses. Assays for uterine expression of the genes Hoxa10, Hoxa11, and Wnt7a shortly after treatment indicated significant decreases in DES-treated wild-type but no effect in the αERKO. In contrast, the DES effect on uterine expression of Wnt4 and Wnt5a was preserved in both genotypes, suggesting a developmental role for ERβ. Adult αERKO mice exhibited complete resistance to the chronic effects of neonatal DES exposure exhibited in treated wild-type animals, including atrophy, decreased weight, smooth muscle disorganization, and epithelial squamous metaplasia in the uterus; proliferative lesions of the oviduct; and persistent vaginal cornification. Therefore, the lack of DES effects on gene expression and tissue differentiation in the αERKO provides unequivocal evidence of an obligatory role for ERα in mediating the detrimental actions of neonatal DES exposure in the murine reproductive tract
Diverse Genes Expressed in Distinct Regions of the Trunk Epithelium Define a Monolayer Cellular Template for Construction of the Oikopleurid House

AbstractThe filter-feeding house secreted by urochordate Appendicularians is among the most complex extracellular structures constructed by any organism. This structure allows the Appendicularia to exploit a wide range of food particle sizes, including nanoplankton and submicrometer colloids, establishing them as an important and abundant component of marine zooplankton communities throughout the world. The oikoplastic epithelium, a monolayer of cells covering the trunk of the animal, is responsible for secretion of the house. The epithelium has a fixed number of cells, organized in distinct fields, characterized by defined cell shapes and nuclear morphologies. Certain structures in the house appear to be spatially linked to these different fields of cells. Using cDNA representation difference analysis (cDNA RDA) on whole animals at two different developmental stages separated by the metamorphic tailshift event, we isolated four families of genes (oikosins) that are expressed only from specific subregions of the oikoplastic epithelium. The molecular patterns defined by oikosin gene expression establish the epithelium as an ideal and easily accessible monolayer cellular template for exploring coordinate regulation of gene expression, cell–cell interactions involved in pattern formation, gene/genome amplification, and the role of temporal changes in nuclear architecture in regulating gene expression
Syndecan-3 and Syndecan-4 Specifically Mark Skeletal Muscle Satellite Cells and Are Implicated in Satellite Cell Maintenance and Muscle Regeneration

AbstractMyogenesis in the embryo and the adult mammal consists of a highly organized and regulated sequence of cellular processes to form or repair muscle tissue that include cell proliferation, migration, and differentiation. Data from cell culture and in vivo experiments implicate both FGFs and HGF as critical regulators of these processes. Both factors require heparan sulfate glycosaminoglycans for signaling from their respective receptors. Since syndecans, a family of cell-surface transmembrane heparan sulfate proteoglycans (HSPGs) are implicated in FGF signaling and skeletal muscle differentiation, we examined the expression of syndecans 1–4 in embryonic, fetal, postnatal, and adult muscle tissue, as well as on primary adult muscle fiber cultures. We show that syndecan-1, -3, and -4 are expressed in developing skeletal muscle tissue and that syndecan-3 and -4 expression is highly restricted in adult skeletal muscle to cells retaining myogenic capacity. These two HSPGs appear to be expressed exclusively and universally on quiescent adult satellite cells in adult skeletal muscle tissue, suggesting a role for HSPGs in satellite cell maintenance or activation. Once activated, all satellite cells maintain expression of syndecan-3 and syndecan-4 for at least 96 h, also implicating these HSPGs in muscle regeneration. Inhibition of HSPG sulfation by treatment of intact myofibers with chlorate results in delayed proliferation and altered MyoD expression, demonstrating that heparan sulfate is required for proper progression of the early satellite cell myogenic program. These data suggest that, in addition to providing potentially useful new markers for satellite cells, syndecan-3 and syndecan-4 may play important regulatory roles in satellite cell maintenance, activation, proliferation, and differentiation during skeletal muscle regeneration
The Combinatorial Activities of Nkx2.5 and dHAND Are Essential for Cardiac Ventricle Formation

AbstractNkx2.5/Csx and dHAND/Hand2 are conserved transcription factors that are coexpressed in the precardiac mesoderm and early heart tube and control distinct developmental events during cardiogenesis. To understand whether Nkx2.5 and dHAND may function in overlapping genetic pathways, we generated mouse embryos lacking both Nkx2.5 and dHAND. Mice heterozygous for mutant alleles of Nkx2.5 and dHAND were viable. Although single Nkx2.5 or dHAND mutants have a morphological atrial and single ventricular chamber, Nkx2.5−/−dHAND−/− mutants had only a single cardiac chamber which was molecularly defined as the atrium. Complete ventricular dysgenesis was observed in Nkx2.5−/−dHAND−/− mutants; however, a precursor pool of ventricular cardiomyocytes was identified on the ventral surface of the heart tube. Because Nkx2.5 mutants failed to activate eHAND expression even in the early precardiac mesoderm, the Nkx2.5−/−dHAND−/− phenotype appears to reflect an effectively null state of dHAND and eHAND. Cell fate analysis in dHAND mutants suggests a role of HAND genes in survival and expansion of the ventricular segment, but not in specification of ventricular cardiomyocytes. Our molecular analyses also revealed the cooperative regulation of the homeodomain protein, Irx4, by Nkx2.5 and dHAND. These studies provide the first demonstration of gene mutations that result in ablation of the entire ventricular segment of the mammalian heart, and reveal essential transcriptional pathways for ventricular formation
How the Zebrafish Gets Its Stripes

AbstractThe study of vertebrate pigment patterns is a classic and enduring field of developmental biology. Knowledge of pigment pattern development comes from a variety of systems, including avians, mouse, and more recently, the zebrafish (Danio rerio). Recent analyses of the mechanisms underlying the development of the neural crest-derived pigment cell type common to all vertebrates, the melanocyte, have revealed remarkable similarities and several surprising differences between amniotes and zebrafish. Here, we summarize recent advances in the study of melanocyte development in zebrafish, with reference to human, mouse, and avian systems. We first review melanocyte development in zebrafish and mammals, followed by a summary of the molecules known to be required for their development. We then discuss several relatively unaddressed issues in vertebrate pigment pattern development that are being investigated in zebrafish. These include determining the relationships between genetically distinct classes of melanocytes, characterizing and dissecting melanocyte stem cell development, and understanding how pigment cells organize into a patterned tissue. Further analysis of zebrafish pigment pattern mutants as well as new generations of directed mutant screens promise to extend our understanding of pigment pattern morphogenesis
A Spontaneous Mouse Mutation, mesenchymal dysplasia (mes), Is Caused by a Deletion of the Most C-Terminal Cytoplasmic Domain of patched (ptc)

AbstractA recessive mouse mutation, mesenchymal dysplasia (mes), which arose spontaneously on Chromosome 13, causes excess skin, increased body weight, and mild preaxial polydactyly. Fine gene mapping in this study indicated that mes is tightly linked to patched (ptc) that encodes a transmembrane receptor protein for Shh. Molecular characterization of the ptc gene of the mes mutant and an allelism test using a ptc knockout allele (ptc−) demonstrated that mes is caused by a deletion of the most C-terminal cytoplasmic domain of the ptc gene. Since mes homozygous embryos exhibit normal spinal cord development as compared with ptc− homozygotes, which die around 10 dpc with severe neural tube defects, the C-terminal cytoplasmic domain lost in mes mutation is dispensable for inhibition of Shh signaling in early embryogenesis. However, compound heterozygotes of ptc− and mes alleles, which survive up to birth and die neonatally, had increased body weight and exhibited abnormal anteroposterior axis formation of the limb buds. These findings indicate that Ptc is a negative regulator of body weight and ectopic activation of Shh signaling in the anterior mesenchyme of the limb buds, and that the C-terminal cytoplasmic domain of Ptc is involved in its repressive action
Expression Cloning of Xenopus Os4, an Evolutionarily Conserved Gene, which Induces Mesoderm and Dorsal Axis

AbstractMultiple factors, including members of the FGF, TGFβ, and Wnt family of proteins, are important mediators in the regulation of dorsal–ventral pattern formation during vertebrate development. By using an expression cloning approach to identify novel factors that could regulate dorsal–ventral patterning in the Xenopus embryo, we isolated the Xenopus homologue of the human Os4 gene by virtue of its ability to induce a secondary dorsal axis. While Os4 homologues have been identified in a variety of species, and human Os4 is overexpressed in human tumors, the biological function of Os4 is unknown. To explore the mechanism by which Xenopus Os4 (XOs4) induces a secondary dorsal axis, we used Xenopus explant and whole-embryo assays. The secondary axis induced by XOs4 is distinct from that induced by activation of Wnt or FGF pathways but similar to that induced by inhibition of BMP signaling or activation of an Activin pathway. However, XOs4 did not inhibit BMP signaling in dissociated animal cap explants, indicating that XOs4 does not inhibit BMP signaling. Similar to activation of an Activin-like pathway, expression of XOs4 induces molecular markers for mesoderm in animal cap explants, although expression of gastrula-stage mesodermal markers was very weak and substantially delayed. Yet, XOs4 does not require activity of the Activin signal-transduction pathway for mesoderm induction as dominant-negative components of the Activin/Nodal/Vg1 pathway did not prevent XOs4-mediated induction of mesodermal derivatives. Finally, like Activin/Nodal/Vg1 pathways, XOs4 requires FGF signaling for expression of mesoderm markers. Results presented in this study demonstrate that XOs4 can induce mesoderm and dorsalize ventral mesoderm resulting in ectopic dorsal axis formation, suggesting a role for this large evolutionarily conserved gene family in early development
Displacement of the Mitotic Apparatus Which Induces Ectopic Polar Body Formation or Parthenogenetic Cleavage in Starfish Oocytes

AbstractWhen the mitotic apparatus (MA) at meiosis I and II in starfish oocytes was detached from the animal pole and translocated to the other cortex, MA induced polar body formation, which indicates reattachment of MA to the cortex. MA attachment was so strong that MA at meiosis II was frequently broken into two parts during detachment and from the remnant part remaining at the cortex an aster derived and a nucleus derived from the detached part. When they were apart until the cleavage stage, the oocyte divided into the aster-containing and nucleus-containing blastomeres and, further, only the former blastomere divided repeatedly. This result indicates that the centrosome in the peripheral aster, which presumes to be discarded into the second polar body, always has the capacity of duplication but the centrosome in the inner aster, which stays in the oocyte interior, has not the capacity and confirms our previous report (17Dev. Biol. 203, 62–74). Furthermore, it is found by observing meiotic MA formation that this peculiar centrosome delivery at meiosis II is ensured by the fact that the attachment of the aster staying in the oocyte interior to the cortex occurs earlier than centrosome duplication
The Avian Telencephalic Subpallium Originates Inhibitory Neurons That Invade Tangentially the Pallium (Dorsal Ventricular Ridge and Cortical Areas)

AbstractRecent data on the development of the mammalian neocortex support that the majority of its inhibitory GABAergic interneurons originate within the subpallium (ganglionic eminences). Support for such tangential migration into the pallium has come from experiments using fluorescent tracers or lineage analysis with retrovirus, and the phenotypes of mutant mice with different abnormalities in the developing subpallium. In the present study, we describe tangential migration of subpallial-derived neurons in the developing chick telencephalon. Using quail–chick grafts, we precisely identified the neuroepithelial origin, time-course, and pathways of migration, as well as the identity and relative distribution of the diverse tangentially migrated neurons. The analysis of selective grafts of the pallidal and striatal primordia allowed us to determine the relative contribution of each primordium to the population of migrating neurons. Moreover, we found that, like in mammals, the vast majority of the GABAergic and calbindin-immunoreactive neurons within the pallium (dorsal ventricular ridge and cortical areas) have an extracortical, subpallial origin. Our results suggest that the telencephalon of birds and mammals share developmental mechanisms for the origin and migration of their cortical interneurons, which probably first evolved at an earlier stage in the radiation of vertebrates than was thought before
Fate Map of the Avian Anterior Forebrain at the Four-Somite Stage, Based on the Analysis of Quail–Chick Chimeras

AbstractTo better understand the topological organization of the primordia within the anterior forebrain, we made a fate map of the rostral neural plate in the chick. Homotopic grafts at the four-somite stage were allowed to survive for up to 9 days to enable an analysis of definitive brain structures. In some cases, the topography of the grafted neuroepithelia was compared with gene expression patterns. The midpoint of the anterior neural ridge maps upon the anterior commissure in the closed neural tube, continuing concentrically into the preoptic area and optic field. Non-neural epithelium just in front of this median ridge gives rise to the adenohypophysis. Areas for the presumptive pallial commissure, septum, and prosencephalic choroidal tissue lie progressively more posteriorly along the ridge, peripheral to the telencephalic entopeduncular and striatopallidal primordia (the subpallium), and the pallium (olfactory bulb, dorsal ventricular ridge, and cortical domains). Subpallial structures lie topologically anterior to the pallial formations, and both are concentric to the septum. Within the pallium, the major cortical domains (Wulst and caudolateral, parahippocampal, and hippocampal cortices) appear posterior to the dorsal ventricular ridge. The amygdaloid region appears concentrically across both the subpallial and pallial regions. This fate map shows that the arrangement of the prospective primordia in the neural plate is basically a flattened representation of topological relationships present in the mature brain, though marked phenomena of differential growth and selective tangential migration of some cell populations complicate the histogenetic constitution of the mature telencephalon