bluuebunny/crossref_metadata_2025_split huggingface dataset:
Astroglial control of oligodendrocyte survival mediated by PDGF and Leukemia Inhibitory Factor-like protein
Authors: Gard A. L. , Burrell M. R. , Pfeiffer S. E. , Rudge J. S. , Williams W. C. 
Published: April 2021

ABSTRACT
Programmed death and the identification of growth factors delaying this process in the oligodendrocyte lineage suggest that other cell types provide oligodendrogliotrophins. To determine their source, primary cultures of oligodendroblasts immunopurified from postnatal rat cerebrum were used to screen other cultured neural and non-neural cell types for the release of survival factors into a defined insulin-containing medium. In non-conditioned medium, oligodendroblasts died 1-2 days after undergoing terminal differentiation into oligodendrocytes, as defined by the onset of expression of galactocerebroside. In medium conditioned by astrocytes, unlike the other tested cell types, differentiated oligodendrocytes survived for weeks in a mature myelinogenic state. Survival was partially reduced by immunoabsorption of the medium with antibodies to platelet-derived growth factor and abolished by immunoabsorption with antibodies to leukemia inhibitory factor. By the same criterion, survival activity was not attributed to other astrocytic products, ciliary neurotrophic factor and basic fibroblast growth factor. Membrane ultrafiltration analysis indicated the activity corresponded to heat-labile protein smaller (Mr = 10-30×103) than native rat leukemia inhibitory factor (Mr = 43×103). The astrocytic stimulus was &gt;4-fold more efficacious than other known oligodendrogliotrophic cytokines, including ciliary neurotrophic factor, neurotrophin-3 and leukemia inhibitory factor itself, tested singly or in combination, and promoted survival additively with these agents. These findings suggest that astrocytes function as paracrine regulators of oligodendroblast and oligodendrocyte survival and that their effect is mediated initially by platelet-derived growth factor and thereafter by a powerful cytokine related to leukemia inhibitory factor.
The Breathless FGF receptor homolog, a downstream target of Drosophila C/EBP in the developmental control of cell migration
Authors: Murphy Anne Marie , Lee Tzumin , Andrews Cynthia M. , Shilo Ben-Zion , Montell Denise J. 
Published: April 2021

ABSTRACT
To investigate the molecular mechanisms responsible for the temporal and spatial control of cell movements during development, we have been studying the migration of a small group of follicle cells, called the border cells, in the Drosophila ovary. Timely initiation of border cell migration requires the product of the slow border cells (slbo) locus, which encodes the Drosophila homolog of the transcription factor C/EBP. Here we report evidence that one target of C/EBP in the control of border cell migration is the FGF receptor homolog encoded by the breathless (btl) locus. btl expression in the ovary was border cell-specific, beginning just prior to the migration, and this expression was reduced in slbo mutants. btl mutations dominantly enhanced the border cell migration defects found in weak slbo alleles. Furthermore, C/EBP-independent btl expression was able to rescue the migration defects of hypomorphic slbo alleles. Purified Drosophila C/EBP bound eight sites in the btl 5′ flanking region by DNAse I footprinting. Taken together these results suggest that btl is a key, direct target for C/EBP in the regulation of border cell migration.
wingless and patched are negative regulators of the morphogenetic furrow and can affect tissue polarity in the developing Drosophila compound eye
Authors: Ma Chaoyong , Moses Kevin 
Published: April 2021

ABSTRACT
In the developing Drosophila compound eye, a wave of pattern formation and cell-type determination sweeps across the presumptive eye epithelium. This ‘morpho-genetic furrow’ coordinates the epithelial cells’ division cycle, shape and gene expression to produce evenly spaced neural cell clusters that will eventually form the adult ommatidia. As these clusters develop, they rotate inwards to face the eye’s equator and establish tissue polarity. We have found that wingless is strongly expressed in the dorsal margin of the presumptive eye field, ahead of the morpho-genetic furrow. We have shown that inactivation of Wingless results in the induction of an ectopic furrow that proceeds ventrally from the dorsal margin. This ectopic furrow is normal in most respects, however the clusters formed by it fail to rotate, and we propose a two-vector model to account for normal rotation and tissue polarity in the retina. A second consequence of this inactivation of Wingless is that the dorsal head is largely deleted. We have also found that patched loss-of-function mosaic clones induce circular ectopic morphogenetic furrows (consistent with the observations of other workers with the hedgehog, and PKA genes). We use such patched induced furrows to test the two-vector model for cluster rotation and tissue polarity.
Patterns of free calcium in multicellular stages of Dictyostelium expressing jellyfish apoaequorin
Authors: Cubitt Andrew B. , Firtel Richard A. , Fischer Gabriele , Jaffe Lionel F. , Miller Andrew L. 
Published: April 2021

ABSTRACT
To examine the patterns of high free cytosolic calcium or [Ca2+]i during Dictyostelium’s development, we expressed apoaequorin in D. discoideum, reconstituted aequorin and observed the resultant patterns of calcium-dependent luminescence. Specific, high calcium zones are seen throughout normal multicellular development and are roughly coincident with those regions that later differentiate into stalk or stalk-like cells. A slug, for example, shows a primary high calcium zone within its front quarter and a secondary one around its tail; while a mound shows such a zone around the periphery of its base. Combined with previous evidence, our findings support the hypothesis that high [Ca2+]i feeds back to favor the stalk pathway.
We also discovered several high calcium zones within the mound’s base that do not coincide with any known prepatterns in D. discoideum. These include two, relatively persistent, antipodal strips along the mound’s periphery.
These various persistent zones of high calcium are largely made up of frequent, 10 to 30 second long, semi-periodic calcium spikes. Each of these spikes generates a correspondingly short-lived, 200 to 500 μm long, high calcium band which extends along the nearby surface. Similar, but relatively large and infrequent, spikes generate cross bands which extend across migrating slugs and just behind their advancing tips as well as across the peripheries of rotating mounds and midway between their antipodal strips. Moreover, calcium has a doubling time of about a second as various spikes rise. This last observation suggests that the calcium bands seen in Dictyostelium may be generated by so-called fast calcium waves.
Initiation of cardiac differentiation occurs in the absence of anterior endoderm
Authors: Gannon Maureen , Bader David 
Published: April 2021

ABSTRACT
Anterior endoderm has been proposed to be a specific inducer of cardiac differentiation in vertebrates (reviewed in Jacobson and Sater, Development 104, 341-359, 1988). The ability of cardiogenic mesoderm to differentiate in a minimal culture system was examined using cardiac-specific gene expression as an assay. Anterior lateral plate mesoderm was explanted from chick embryos with and without associated endoderm at developmental stages from just after gastrulation (stage 4; Hamburger and Hamilton, J. Morph. 88, 49-67, 1951) to just prior to contraction (stage 9). At all stages examined, cardiogenic mesoderm expressed a profile of cardiac-specific mRNAs after two days in minimal medium independent of the presence of endoderm. Our studies indicate that endoderm is necessary for the generation of stable sarcomeric protein expression, organized myofibrils and beating tissue from stage 4-6. Subsequent to this stage, an interaction with anterior endoderm is no longer required. Examination of cardia bifida embryos from which anterior endoderm had been unilaterally removed also showed a stage-dependent effect of endoderm on beating, while cardiac gene expression and heart morphogenesis were unaffected. These results demonstrate that anterior endoderm does not induce or maintain cardiac gene expression, nor is it required for terminal differentiation. Endoderm does appear to be necessary for a short period of time between initiation of cardiac gene expression and the onset of contraction.
Distribution of Sonic hedgehog peptides in the developing chick and mouse embryo
Authors: Martí Elisa , Takada Ritsuko , Bumcrot David A. , Sasaki Hiroshi , McMahon Andrew P. 
Published: April 2021

ABSTRACT
Sonic hedgehog (Shh) encodes a signal that is implicated in both short-and long-range interactions that pattern the vertebrate central nervous system (CNS), somite and limb. Studies in vitro indicate that Shh protein undergoes an internal cleavage to generate two secreted peptides. We have investigated the distribution of Shh peptides with respect to these patterning events using peptide-specific antibodies. Immunostaining of chick and mouse embryos indicates that Shh peptides are expressed in the notochord, floor plate and posterior mesenchyme of the limb at the appropriate times for their postulated patterning functions. The amino peptide that is implicated in intercellular signaling is secreted but remains tightly associated with expressing cells. The distribution of peptides in the ventral CNS is polarized with the highest levels of protein accumulating towards the luminal surface. Interestingly, Shh expression extends beyond the floor plate, into ventrolateral regions from which some motor neuron precursors are emerging. In the limb bud, peptides are restricted to a small region of posterior-distal mesenchyme in close association with the apical ectodermal ridge; a region that extends 50-75 μm along the anterior-posterior axis. Temporal expression of Shh peptides is consistent with induction of sclerotome in somites and floor plate and motor neurons in the CNS, as well as the regulation of anterior-posterior polarity in the limb. However, we can find no direct evidence for long-range diffusion of the 19×103Mr peptide which is thought to mediate both short-and long-range cell interactions. Thus, either long-range signaling is mediated indirectly by the activation of other signals, or alternatively the low levels of diffusing peptide are undetectable using available techniques.
Innervation is essential for the development and differentiation of a sex-specific adult muscle in Drosophila melanogaster
Authors: Currie Douglas A. , Bate Michael 
Published: April 2021

ABSTRACT
The adult abdominal muscles in Drosophila are generated de novo during metamorphosis and form a simple and characteristic pattern. Throughout adult abdominal development there is a close association between nerves and myoblasts. However, the role of innervation in adult myogenesis is unclear. In males there is an additional muscle, which is unique to abdominal segment 5 (A5). This male specific muscle forms from the same pool of myoblasts as other dorsal muscles in A5 but develops several distinctive characteristics. Previous work indicates the genotype of the innervation of this male specific muscle may play a crucial role in its proper development, although the part played by innervation in the development of other muscles is unknown. Here we test directly the function of innervation in adult myogenesis in general and for the development and differentiation of the male specific muscle in particular. After denervation at the onset of metamorphosis, muscle growth is impaired although the overall muscle pattern continues to develop. Uniquely, the male specific muscle fails to form. Our results indicate that there is an essential role for innervation during the period of metamorphosis for the formation of a full complement of abdominal muscles and for muscle growth. Furthermore, innervation is absolutely required for the formation of the male specific muscle and the development of its special characteristics.
Cranial paraxial mesoderm and neural crest cells of the mouse embryo: co-distribution in the craniofacial mesenchyme but distinct segregation in branchial arches
Authors: Trainor Paul A. , Tam Patrick P. L. 
Published: April 2021

ABSTRACT
The spatial distribution of the cranial paraxial mesoderm and the neural crest cells during craniofacial morphogenesis of the mouse embryo was studied by micromanipulative cell grafting and cell labelling. Results of this study show that the paraxial mesoderm and neural crest cells arising at the same segmental position share common destinations. Mesodermal cells from somitomeres I, III, IV and VI were distributed to the same craniofacial tissues as neural crest cells of the forebrain, the caudal midbrain, and the rostral, middle and caudal hindbrains found respectively next to these mesodermal segments. This finding suggests that a basic meristic pattern is established globally in the neural plate ectoderm and paraxial mesoderm during early mouse development. Cells from these two sources mixed extensively in the peri-ocular, facial, periotic and cervical mesenchyme. However, within the branchial arches a distinct segregation of these two cell populations was discovered. Neural crest cells colonised the periphery of the branchial arches and enveloped the somitomere-derived core tissues on the rostral, lateral and caudal sides of the arch. Such segregation of cell populations in the first three branchial arches is apparent at least until the 10.5-day hindlimb bud stage and could be important for the patterning of the skeletal and myogenic derivatives of the arches.
Cloning and characterization of a second AP-2 transcription factor: AP-2β
Authors: Moser Markus , Imhof Axel , Pscherer Armin , Bauer Reinhard , Amselgruber Werner , Sinowatz Fred , Hofstädter Ferdinand , Schüle Roland , Buettner Reinhard 
Published: April 2021

ABSTRACT
AP-2 has been characterized previously as a unique 52×103Mr transcription activator encoded by a single gene that is expressed in a restricted pattern during embryonic morphogenesis of the peripheral nervous system, face, skin and nephric tissues. Here we report the isolation of genomic and cDNA clones encoding for a second AP-2 related transcription factor, designated AP-2β. AP-2β binds specifically to a series of well-characterized AP-2 binding sites, consensus to the sequence G/CCCN3GGC, and transactivates transcription from a reporter plasmid under the control of an AP-2-dependent promoter. A C-terminal domain known to mediate homodimerization of the previously cloned AP-2α transcription activator is highly conserved and sufficient to mediate interaction between the two proteins. Northern blot and in situ hybridizations revealed that the two genes are expressed in murine embryos between days 9.5 and 19.5 p.c. Coexpression of both mRNAs was detected in many tissues at day 13.5 and 15.5 of embryogenesis but some regions of the developing brain and face including the primordium of midbrain and the facial mesenchyme differed in their expression pattern of AP-2 genes. AP-2α and AP-2β signals in the central and peripheral nervous system overlapped with regions of developing sensory neurons. In adult tissues AP-2α expression was found mainly in the skin, eye and prostate and AP-2β expression in the kidney. In summary, our analyses of embryonic and adult mice demonstrate that two different AP-2 transcription factors are specifically expressed during differentiation of many neural, epidermal and urogenital tissues.
A biochemical model for the initiation and maintenance of the quiescent center: implications for organization of root meristems
Authors: Kerk Nancy M. , Feldman Lewis J. 
Published: April 2021

ABSTRACT
A new hypothesis for the formation of the quiescent center is presented. Reported data support a mechanism for the establishment and maintenance of the quiescent center. The quiescent center is located at the most distal part of the root proper, the most terminal location in the root proper on the path of polar transport from the shoot. Of the many substances polarly transported in the root, auxin is one of the best studied and has been shown to affect root meristem organization. In our mechanism, polar auxin is directly linked to quiescence through the action of ascorbate oxidase and ascorbic acid. Immunolocalization of auxin in the root tip of Zea mays showed that auxin levels in the quiescent center were high compared to the levels in the immediately surrounding meristematic cells. Isolated quiescent centers were shown to have high levels of ascorbate oxidase mRNA and ascorbate oxidase activity relative to proximal meristem tissue. Exogenous auxin caused an increase in ascorbate oxidase mRNA levels and ascorbate oxidase enzyme activity in cultured root tissue. Immunolocalization of ascorbate oxidase in Zea root tips showed high levels of the protein in the quiescent center relative to surrounding cells. This is the first report of a positive marker and activity for the quiescent center. Histochemical detection of ascorbic acid in Zea root tips showed that quiescent center cells have low or undetectable levels of ascorbic acid, presumably due to the high levels of ascorbate oxidase in the quiescent center. As ascorbic acid is a compound known to be necessary for the transition from G1 to S in the cell cycle, its low levels in the quiescent center may be directly responsible for holding these rarely dividing cells in the extended G1 state in which they are mainly found. We propose that our mechanism complements published mathematical modeling of the anatomical structure of root apices, and further propose that the control of relative growth rates in this focal region of the root apex by this mechanism is a determining aspect in generating anatomical patterning in the root apex.
Function of the Polycomb protein is conserved in mice and flies
Authors: Müller Jürg , Gaunt Stephen , Lawrence Peter A. 
Published: April 2021

ABSTRACT
A key aspect of determination — the acquisition and propagation of cell fates — is the initiation of patterns of selector gene expression and their maintenance in groups of cells as they divide and develop. In Drosophila, in those groups of cells where particular selector genes must remain inactive, it is the Polycomb-Group of genes that keep them silenced. Here we show that M33, a mouse homologue of the Drosophila Polycomb protein, can substitute for Polycomb in transgenic flies. Polycomb protein is thought to join with other Polycomb-Group proteins to build a complex that silences selector genes. Since members of this group of proteins have their homologues in mice, our results suggest that the molecular mechanism of cell determination is widely conserved.
Functional analysis of the Antirrhinum floral homeotic DEFICIENS gene in vivo and in vitro by using a temperature-sensitive mutant
Authors: Zachgo Sabine , Andrade Silva Eugenia de , Motte Patrick , Tröbner Wolfgang , Saedler Heinz , Schwarz-Sommer Zsuzsanna 
Published: April 2021

ABSTRACT
Flowers of the temperature-sensitive DEFICIENS (DEF) mutant, def-101, display sepaloid petals and carpelloid stamens when grown at 26°C, the non-permissive temperature. In contrast, when cultivated under permissive conditions at 15°C, the morphology of def-101 flowers resembles that of the wild type. Temperature shift experiments during early and late phases of flower development revealed that second and third whorl organ development is differentially sensitive to changes in DEF expression. In addition, early DEF expression seems to control the spatially correct initiation of fourth whorl organ development. Reduction of the def-101 gene dosage differentially affects organogenesis in adjacent whorls: at the lower temperature development of petals in the second whorl and initiation of carpels in the centre of the flower is not affected while third whorl organogenesis follows the mutant (carpelloid) pattern. The possible contribution of accessory factors to organ-specific DEF functions is discussed. In situ analyses of mRNA and protein expression patterns during def-101 flower development at 15°C and at 26°C support previously proposed combinatorial regulatory interactions between the MADS-box proteins DEF and GLOBOSA (GLO), and provide evidence that the autoregulatory control of DEF and GLO expression by the DEF/GLO heterodimer starts after initiation of all organ primordia. Immunolocalisation revealed that both proteins are located in the nucleus. Interestingly, higher growth temperature affects the stability of both the DEF-101 and GLO proteins in vivo. In vitro DNA binding studies suggest that the temperature sensitivity of the def-101 mutant is due to an altered heterodimerisation/DNA-binding capability of the DEF-101 protein, conditioned by the deletion of one amino acid within the K-box, a protein region thought to be involved in protein-protein interaction. In addition, we introduce a mutant allele of GLO, glo-confusa, where insertion of one amino acid impairs the hydrophobic carboxy-terminal region of the MADS-box, but which confers no strong phenotypic changes to the flower. The strong mutant phenotype of flowers of def-101/glo-conf double mutants when grown in the cold represents genetic evidence for heterodimerisation between DEF and GLO in vivo. The potential to dissect structural and functional domains of MADS-box transcription factors is discussed.
Temporally restricted spatial localization of acetylated isoforms of histone H4 and RNA polymerase II in the 2-cell mouse embryo
Authors: Worrad Diane M. , Turner Bryan M. , Schultz Richard M. 
Published: April 2021

ABSTRACT
Using immunofluorescent labeling and laser-scanning confocal microscopy, we show that isoforms of histone H4 acetylated on lysine 5, 8 and/or 12 (H4.Ac5-12), as well as RNA polymerase II, become enriched at the nuclear periphery around the time of zygotic gene activation, i.e., the 2-cell stage, in the preimplantation mouse embryo. In contrast, DNA and H4 acetylated on lysine 16 are uniformly distributed throughout the cytoplasm. Culture of embryos with inhibitors of histone deacetylase tricho-statin A and trapoxin results in an increase in the (1) amount of acetylated histone H4 detected by immunoblotting, (2) intensity and sharpness of the peripheral staining for H4.Ac5-12, and (3) relative rate of synthesis of proteins that are markers for zygotic gene activation. The enhanced staining for H4.Ac5-12 at the nuclear periphery seems to require DNA replication, but appears independent of cytokinesis or transcription, since its development is inhibited by aphidicolin but not by either cytochalasin D or α-amanitin. Lastly, the restricted localization of H4.Ac 5-12 is not observed in the 4-cell embryo or at later stages of preimplantation development. These results suggest that changes in chromatin structure underlie, at least in part, zygotic gene activation in the mouse.
goosecoid is not an essential component of the mouse gastrula organizer but is required for craniofacial and rib development
Authors: Rivera-Pérez Jaime A. , Mallo Moisés , Gendron-Maguire, Maureen , Gridley Thomas , Behringer Richard R. 
Published: April 2021

ABSTRACT
goosecoid (gsc) is an evolutionarily conserved homeobox gene expressed in the gastrula organizer region of a variety of vertebrate embryos, including zebrafish, Xenopus, chicken and mouse. To understand the role of gsc during mouse embryogenesis, we generated gsc-null mice by gene targeting in embryonic stem cells. Surprisingly, gsc-null embryos gastrulated and formed the primary body axes; gsc-null mice were born alive but died soon after birth with numerous craniofacial defects. In addition, rib fusions and sternum abnormalities were detected that varied depending upon the genetic background. Transplantation experiments suggest that the ovary does not provide gsc function to rescue gastrulation defects. These results demonstrate that gsc is not essential for organizer activity in the mouse but is required later during embryogenesis for craniofacial and rib cage development.