bluuebunny/crossref_metadata_2025_split huggingface dataset:
Postimplantation expression patterns indicate a role for the mouse forkhead/HNF-3 α, β and γ genes in determination of the definitive endoderm, chordamesoderm and neuroectoderm
Authors: Monaghan A. Paula , Kaestner Klaus H. , Grau Evelyn , Schütz Günther 
Published: April 2021

ABSTRACT
The HNF-3 α, β and γ genes constitute a family of transcription factors that are required for hepatocytespecific gene expression of a number of genes, e.g. transthyretin, α-1 antitrypsin and tyrosine aminotransferase. These genes share a highly conserved DNA-binding domain first found in the Drosophila gene, forkhead, which is required for the normal patterning of the developing gut and central nervous system in Drosophila. In adult mouse tissues, transcripts from HNF-3 αand β have been localised to the liver, intestine and lung, whereas HNF-3 γ is found in the liver, intestine and testis. In light of the early developmental significance of forkhead in Drosophila, we have compared the patterns of expression of HNF-3 α, β and γ mRNAs during murine embryogenesis. We find that these genes are sequentially activated during development in the definitive endoderm. HNF-3 β mRNA is expressed in the node at the anterior end of the primitive streak in all three germ layers and is the first gene of this family to be activated. Subsequently, HNF-3 α is transcribed in the primitive endoderm in the region of the invaginating foregut and HNF-3 γ appears upon hindgut differentiation. These genes have different anterior boundaries of mRNA expression in the developing endoderm and transcripts are found in all endoderm-derived structures that differentiate posterior to this boundary. Therefore, we propose that these genes define regionalisation within the definitive endoderm. Furthermore, differential mRNA expression of HNF-3 α and β is detected in cells of the ventral neural epithelium, chordamesoderm and notochord. In the neural epithelium, expression of HNF-3 αand β mRNA becomes localised to cells of the floor plate. We propose that, in addition to their characterised requirement for liver-specific gene expression, HNF-3 αand γ are required for mesoderm and neural axis formation. We also conclude that HNF-3 β is the true orthologue of the Drosophila forkhead gene.
Sympathetic neuroblasts undergo a developmental switch in trophic dependence
Authors: Birren Susan J. , Lo Liching , Anderson David J. 
Published: April 2021

ABSTRACT
Sympathetic neurons require NGF for survival, but it is not known when these cells first become dependent on neurotrophic factors. We have examined in vitro mitotically active sympathetic neuroblasts immuno-isolated from different embryonic stages, and have correlated this functional data with the expression of neurotrophin receptor mRNAs in vivo. Cells from E14.5 ganglia are supported by neurotrophin-3 (NT-3) in a serum-free medium, but not by NGF; NT-3 acts as a bona fide survival factor for these cells and not simply as a mitogen. By birth, sympathetic neurons are well supported by NGF, whereas NT-3 supports survival only weakly and at very high doses. This change in neurotrophin-responsiveness is correlated with a reciprocal switch in the expression of trkC and trkA mRNAs by sympathetic neuroblasts in vivo. These data suggest that neurotrophic factors may control neuronal number at earlier stages of development than previously anticipated. They also suggest that the acquisition of NGF-dependence may occur, at least in part, through the loss of receptors for these interim survival factors.
The migrational patterns and developmental fates of glial precursors in the rat subventricular zone are temporally regulated
Authors: Levison Steven W. , Chuang Cathy , Abramson Bernetta J. , Goldman James E. 
Published: April 2021

ABSTRACT
Postnatal gliogenesis in the rodent forebrain was studied by infecting subventricular zone cells of either neonates or juvenile rats with replication-deficient retroviruses that encode reporter enzymes, enabling the migration and fate of these germinal zone cells to be traced over the ensuing several weeks. Neither neonatal nor juvenile subventricular zone cells migrated substantially along the rostral-caudal axis. Neonatal subventricular zone cells migrated dorsally and laterally into hemispheric gray and white matter and became both astrocytes and oligodendrocytes. Juvenile subventricular zone cells migrated into more medial areas of the subcortical white matter and on occasion appeared in the white matter of the contralateral hemisphere, but rarely migrated into the neocortex. Juvenile subventricular zone cells almost exclusively differentiated into oligodendrocytes. Thus, the migratory patterns and the developmental fates of subventricular zone cells change during the first 2 weeks of life. When either neonatal or juvenile subventricular zone cells were labeled in vivo and then removed and cultured, some generated homogeneous clones that contained either astrocytes with a ‘type 1’ phenotype or oligodendrocytes, but some generated heterogeneous clones that contained both glial types. These results provide additional evidence for a common progenitor for astrocytes and oligodendrocytes and strongly suggest that temporally and spatially regulated environmental signals control the destiny of glial progenitors during postnatal development.
A Drosophila G1-specific cyclin E homolog exhibits different modes of expression during embryogenesis
Authors: Richardson Helena E. , O’Keefe Louise V. , Reed Steven I. , Saint Robert 
Published: April 2021

ABSTRACT
We have isolated a Drosophila homolog of the human G1-specific cyclin E gene. Cyclin E proteins thus constitute an evolutionarily conserved subfamily of metazoan cyclins. The Drosophila cyclin E gene, DmcycE, encodes two proteins with a common C-terminal region and unique N-terminal regions. Unlike other Drosophila cyclins, DmcycE exhibits a dynamic pattern of expression during development. DmcycE is supplied maternally, but at the completion of the cleavage divisions and prior to mitosis 14, the maternal transcripts are rapidly degraded in all cells except the pole (germ) cells. Two modes of DmcycE expression are observed in the subsequent divisions. During cycles 14, 15 and 16 in non-neural cells, DmcycE mRNA levels show no cell-cycle-associated variation. DmcycE expression in these cells is therefore independent of the cell cycle phase. In contrast, expression in proliferating embryonic peripheral nervous system cells occurs during interphase as a brief pulse that initiates before and overlaps with S phase, demonstrating the presence of a G1 phase in these embryonic neural cell cycles. DmcycE appears not to be expressed in cells that undergo endoreplication cycles during polytenization. The structural homology to human cyclin E, the ability of DmcycE to rescue a G1 cyclin-deficient yeast strain, the presence of multiple PEST sequences characteristic of G1-specific cyclins and expression during G1 phase in proliferating peripheral nervous system cells all argue that Drosophila cyclin E is a G1 cyclin. Constitutive DmcycE expression in embryonic cycles lacking a G1 phase, in contrast to expression during the G1-S phase transition in cycles exhibiting a G1 phase, implicates DmcycE expression in the regulation of the G1 to S phase transition during Drosophila embryogenesis.
Pax-2 is required for mesenchyme-to-epithelium conversion during kidney development
Authors: Rothenpieler Uwe W. , Dressler Gregory R. 
Published: April 2021

ABSTRACT
The conversion of mesenchyme to epithelium during the embryonic development of the mammalian kidney requires reciprocal inductive interactions between the ureter and the responding metanephric mesenchyme. The Pax-2 gene is activated in the mesenchyme in response to induction and is subsequently down-regulated in more differentiated cells derived from the mesenchyme. Pax-2 belongs to a family of genes, at least three of which encode morphogenetic regulatory transcription factors. In order to determine the role of Pax-2 during kidney development, we have generated a loss-of-function phenotype using antisense oligonucleotides in mouse kidney organ cultures. These oligonucleotides can specifically inhibit Pax-2 protein accumulation in kidney mesenchyme cells, where the intracellular concentrations are maximal. The kidney organ cultures were stained with uvomurulin and laminin antibodies as markers for epithelium formation. With significantly reduced Pax-2 protein levels, kidney mesenchyme cells fail to aggregate and do not undergo the sequential morphological changes characteristic of epithelial cell formation. The data demonstrate that Pax-2 function is required for the earliest phase of mesenchyme-to-epithelium conversion.
Spacing ensures autonomous expression of different stripe enhancers in the even-skipped promoter
Authors: Small Stephen , Arnosti David N. , Levine Michael 
Published: April 2021

ABSTRACT
The even-skipped (eve) promoter contains a series of enhancers that control the expression of different seg-mentation stripes in the Drosophila embryo. The stripe 3 enhancer is located 1.7 kb upstream of the stripe 2 enhancer. Here we demonstrate that these enhancers must be physically separated by a minimum distance for proper stripe expression. When they are directly coupled in either orientation, the enhancers generate abnormal patterns of expression in the early embryo. For example, the levels of stripe 2 expression are augmented and there is a posterior expansion of the pattern when the stripe 3 enhancer is positioned immediately upstream of the stripe 2 enhancer. Despite this spacing requirement, the order of the enhancers within the eve promoter can be reversed without affecting the normal expression pattern. These results suggest that spacing maintains the autonomous activities of the stripe enhancers and that interactions between enhancers can generate novel patterns of gene expression.
Pattern formation in the limbs of Drosophila: bric à brac is expressed in both a gradient and a wave-like pattern and is required for specification and proper segmentation of the tarsus
Authors: Godt Dorothea , Couderc Jean-Louis , Cramton Sarah E. , Laski Frank A. 
Published: April 2021

ABSTRACT
We have identified the gene bric à brac and show that it is required for pattern formation along the proximal-distal axis of the leg and antenna of Drosophila. In bric à brac mutant legs, the bristle pattern of the three central tarsal segments is transformed towards the pattern of the most proximal tarsal segment. In addition, bric à brac mutant legs and antennae have segmentation defects. bric à brac encodes a nuclear protein that shares a highly conserved domain with two transcription factors from Drosophila. bric à brac function is dosage dependent and is required in a graded manner for the specification of tarsal segments. The graded requirement for bric à brac correlates with its graded expression pattern, sug-gesting that the concentration of BRIC Á BRAC protein specifies segment identity in the tarsus.
X chromosome retains the memory of its parental origin in murine embryonic stem cells
Authors: Tada Takashi , Tada Masako , Takagi Nobuo 
Published: April 2021

ABSTRACT
A cytogenetic and biochemical study of balloon-like cystic embryoid bodies, formed by newly established embryonic stem (ES) cell lines having a cytogenetically or genetically marked X chromosome, revealed that the paternally derived X chromosome was inactivated in the majority of cells in the yolk sac-like mural region consisting of the visceral endoderm and mesoderm. The nonrandomness was less evident in the more solid polar region containing the ectodermal vesicle, mesoderm and visceral endoderm. Since the same was true in embryoid bodies derived from ES cells at the 30th subculture generation, it was concluded that the imprinting responsible for the preferential inactivation of the paternal X chromosome that was limited to non-epiblast cells of the female mouse embryos, was stably maintained in undifferentiated ES cells. Differentiating epiblast cells should be able to erase or avoid responding to the imprint.
Adult phenotype in the mouse can be affected by epigenetic events in the early embryo
Authors: Reik Wolf , Römer Irmgard , Barton Sheila C. , Surani M. Azim , Howlett Sarah K. , Klose Joachim 
Published: April 2021

ABSTRACT
Major epigenetic modifications apparently occur during early development in the mouse. The factors that induce such modifications are complex and may involve the various components of a zygote. We have started to explore whether changes in the nucleocytoplasmic composition brought about by micromanipulation can induce phenotypic effects through epigenetic modifications. Nucleocytoplasmic hybrids were therefore prepared by transplanting a female pronucleus into a recipient egg from a different genotype. As a result, the maternal genome was of a different genetic background as compared with the egg cytoplasm. Specifically, experimental zygotes had cytoplasm from the inbred strain C57BL/6, a maternal genome from DBA/2, and a paternal genome from C57BL/6 (termed BDB hybrids). The mirror-image combination, termed DBD, was also made. The reconstituted zygotes were transferred to recipients and allowed to develop to term. Mice born from manipulated zygotes showed transcriptional repression and DNA methylation of major urinary protein genes in their liver, as well as growth deficiency resulting in reduced adult body weight. No altered phenotype was observed in controls in which the maternal pronucleus was simply transplanted back into another zygote of the same genetic background. These results clearly demonstrate phenotypic as well as molecular effects on DNA methylation and expression of at least one gene. Phenotype was therefore no longer predicted by genotype as a result of epigenetic modifications in experimental embryos. What precisely triggers the phenotypic and epigenetic changes is unknown, but presumably, nucleocytoplasmic interactions in hybrid zygotes may be partly responsible.
Basic fibroblast growth factor promotes adhesive interactions of neuroepithelial cells from chick neural tube with extracellular matrix proteins in culture
Authors: Kinoshita Yoshito , Kinoshita Chizuru , Heuer Josef G. , Bothwell Mark 
Published: April 2021

ABSTRACT
Fibroblast growth factors have been increasingly assigned mitogenic and trophic roles in embryonic and postnatal development of the nervous system. Little is known, however, of their functional roles in early embryonic neural development at the neural tube stage. We have examined the effect of basic fibroblast growth factor (bFGF) on the adhesive behavior in culture of dissociated brachio-thoracic neural tube cells from 26- to 30-somite stage chick embryos. Cells plated on collagen-coated substratum at a low density attach to the sub-stratum but show poor cell spreading. Addition of bFGF markedly promotes cell spreading, yielding an epithelial morphology. This effect becomes discernible 6-8 hours after cell plating with bFGF and is completed by 24 hours, with half-maximal and maximal effects attained at around 0.4 and 10 ng/ml, respectively. The number of cells remains largely constant up to 24 hours, and then cell survival and/or mitogenic effects of bFGF become apparent. The cell spreading effect is abolished by cyclo-heximide treatment, inhibited by the anti-β1-integrin antibody CSAT, and accompanied by about twofold increases in the expression of β1-integrin and vinculin, components of focal adhesion complexes. Cells cultured with bFGF for 24 hours exhibit enhanced cell attachment and cell spreading with little time lag following cell plating. In earlier embryonic stages, developmentally less mature cells depend much more on bFGF for their cell spreading and survival, while in later stages the cell spreading response to bFGF becomes undetectable as neural tube develops to spinal cord. The cell spreading effect of bFGF is realized on specific extracellular matrix proteins including laminin, fibronectin and collagen, but not on vitronectin, arg-gly-asp peptide (PepTite-2000), poly-L-ornithine or others. These results suggest that, in an early stage of neural tube development, bFGF is involved in the developmental regulation of adhesive interactions between neuroepithelial cells and the extra-cellular matrix, thereby controlling their proliferation, migration and differentiation.
Interacting signalling pathways regulating prestalk cell differentiation and movement during the morphogenesis of Dictyostelium
Authors: Williams Jeff , Hopper Neil , Early Anne , Traynor David , Harwood Adrian , Abe Tomoaki , Simon Marie Noelle , Véron Michel 
Published: April 2021

ABSTRACT
Analysis of the expression patterns of two genes encoding extracellular matrix proteins shows there to be an unexpectedly complex pattern of prestalk cell differentiation and movement during the morphogenesis of Dictyostelium. The organism employs both cell sorting and positional differentiation to generate a patterned structure but these two mechanisms are used at different times during development. During slug formation prestalk cells arise at scattered positions within the aggregate and then move to its apex to form the tip. In contrast, during culmination, stalk cell differentiation occurs in a positionally localized manner at the entrance to the stalk tube.
Two interacting signalling pathways regulate the differentiation of prestalk and stalk cells. Prestalk cell differentiation is induced by DIF, a chlorinated hexaphenone, and a repression mechanism prevents DIF acting to induce premature stalk cell differentiation during slug migration. At culmination intracellular cAMP levels rise, the cAMP dependent protein kinase (PKA) is activated and the block to stalk cell differentiation is lifted. Activation of PKA is also necessary in order that prestalk cells move to the entrance of the stalk tube at culmination. Thus, in Dictyostelium, PKA plays a role both in the regulation of cellular differentiation and in morphogenetic cell movement.
Dissecting the modes of interactions amongst cell adhesion molecules
Authors: Simmons David L. 
Published: April 2021

ABSTRACT
The process of cell adhesion can be mediated by more than 50 molecules. Fortunately, most of these can be grouped into a small number of superfamilies. For example, more than half of all leukocyte adhesion molecules are members of the immunoglobulin super-family. The principles of cell-cell adhesion are reviewed including: kinetics and equilibria; on/off rates; affinities/avidities; homotypic/heterotypic interactions; mapping and delineation of binding sites. These principles are illustrated with two CAMs: firstly the interaction of the homotypic epithelial/myeloid adhesins CD66, and the endothelial adhesin, CD31, and secondly the heterotypic adhesins ICAM-1, 2 and 3, which interact with the leukocyte integrin LFA-1.
Tumor suppressor genes encoding proteins required for cell interactions and signal transduction in Drosophila
Authors: Bryant Peter J. , Watson Kellie L. , Justice Robin W. , Woods Daniel F. 
Published: April 2021

ABSTRACT
Tumor suppressor genes, whose products are required for the control of cell proliferation, have been identified by their mutant phenotype of tissue overgrowth. Here we describe recent work on the molecular identification of tumor suppressor genes that function in two different cell types of the Drosophila larva: the blood cells, and the undifferentiated epithelial cells of developing imaginai discs. Mutations in the aberrant immune responses (air8) gene lead to overproduction and precocious differentiation of blood cells. This gene encodes the Drosophila homolog of human ribosomal protein S6. The mutant phenotype is consistent with a role for S6 in the control of cell proliferation, and is compatible with findings from mammalian cells where alterations in S6 expression and phosphorylation are associated with changes in cell proliferation. Mutations in the dises large (dlg) gene cause neoplastic overgrowth of imaginai discs in the larva. The mutant discs show loss of septate .junctions and of apical-basal cell polarity, and they also lose the ability to differentiate cuticular structures. The d/g protein product (DlgA) is localized at septate junctions between epithelial cells, and cDNA sequencing indicates that the gene product includes a domain with homology to guanylate kinase (GUK). Two mammalian homologs of this gene have been identified, and one of them (PSD-95/SAP90) encodes a component of synaptic densities in the brain: this protein therefore resembles the DlgA protein in being located in a specialized cell junction that functions in information transfer between cells. Mutations in the fat gene cause hyperplastic imaginai disc overgrowth, in which the overgrowing disc tissue retains its epithelial structure and its ability to differentiate. Some of the excess disc tissue is shed as vesicles suggesting a loss of cell adhesion. In support of this hypothesis, the predicted gene product shows homology to cadherins in its extracellular domain. However, the fat protein is much larger than known cadherins. As in human cancer, somatic loss of the normal alleles of tumor suppressor genes can lead to tumor formation in Drosophila; an example of this is provided by the warts (wts) locus. The wts gene was identified by the dramatic overgrowth of mitotic recombination clones that are homozygous for a wts deletion. In these clones the cuticle intrudes between epithelial cells, suggesting an alteration in cell adhesion. The study of these and other tumor suppressor genes in Drosophila is providing new evidence supporting the critical role of cell interactions and specialized apical junctions in controlling epithelial cell proliferation.
Studies on the teratogenic properties of trypan blue and its components in mice
Authors: Barber Aeleta N. , Geer Jack C. 
Published: April 2021

ABSTRACT
The teratogenic activity of the purified components of trypan blue was studied in pregnant mice. The blue component induced abnormalities similar in type and frequency to those caused by the whole dye, and the water-soluble purple fraction exerted a mild teratogenesis when the concentration was increased to 0 · 3 per cent. The sodium hydroxide-soluble purple and red fractions were without harmful effects. The blue and water-soluble purple fractions are absorbed and retained by the endodermal cells of the visceral yolk-sac from the time they become differentiated until term. The dye granules are associated with proteinaceous materials in apical vacuoles in the cytoplasm of these cells. Prior to the closure of the yolk-sac the dye has direct access to the embryo. Microscopic examination of unstained sections at this stage in development reveals a diffuse staining of the embryonic mass immediately adjacent to the visceral endoderm. The suggestion is offered that cessation of the teratogenic activity of the dye after closure of the yolk-sac is due to its retention and inactivation by the cells of the yolk-sac epithelium.