bluuebunny/crossref_metadata_2025_split huggingface dataset:
Embryonic retinoic acid synthesis is essential for heart morphogenesis in the mouse
Authors: Niederreither Karen , Vermot Julien , Messaddeq Nadia , Schuhbaur Brigitte , Chambon Pierre , Dollé Pascal 
Published: April 2021

AbstractRetinoic acid (RA), the active derivative of vitamin A, has been implicated in various steps of cardiovascular development, but its contribution to early heart morphogenesis has not been clearly established in a mammalian system. To block endogenous RA synthesis, we have disrupted the gene encoding RALDH2, the first retinaldehyde dehydrogenase whose expression has been detected during early mouse post-implantation development. We describe here the heart abnormalities of the RA-deficient Raldh2 mutants that die in utero at gestational day 10.5. The embryonic heart tube forms properly, but fails to undergo rightward looping and, instead, forms a medial distended cavity. Expression of early heart determination factors is not altered in mutants, and the defect in heart looping does not appear to involve the Nodal/Lefty/Pitx2 pathway. Histological and molecular analysis reveal distinct anteroposterior components in the mutant heart tube, although posterior chamber (atria and sinus venosus) development is severely impaired. Instead of forming trabeculae, the developing ventricular myocardium consists of a thick layer of loosely attached cells. Ultrastructural analysis shows that most of the ventricular wall consists of prematurely differentiated cardiomyocytes, whereas undifferentiated cells remain clustered rostrally. We conclude that embryonic RA synthesis is required for realization of heart looping, development of posterior chambers and proper differentiation of ventricular cardiomyocytes. Nevertheless, the precise location of this synthesis may not be crucial, as these defects can mostly be rescued by systemic (maternal) RA administration. However, cardiac neural crest cells cannot be properly rescued in Raldh2− /− embryos, leading to outflow tract septation defects.
Inducible nuclear translocation of a STAT protein in Dictyostelium prespore cells: implications for morphogenesis and cell-type regulation
Authors: Dormann Dirk , Abe Tomoaki , Weijer Cornelis J. , Williams Jeffrey 
Published: April 2021

ABSTRACT
Dd-STATa, the Dictyostelium STAT (signal transducer and activator of transcription) protein, is selectively localised in the nuclei of a small subset of prestalk cells located in the slug tip. Injection of cAMP into the extracellular spaces in the rear of the slug induces rapid nuclear translocation of a Dd-GFP:STATa fusion protein in prespore cells surrounding the site of injection. This suggests that cAMP signals that emanate from the tip direct the localised nuclear accumulation of Dd-STATa. It also shows that prespore cells are competent to respond to cAMP, by Dd- STATa activation, and it implies that cAMP signalling is in some way limiting in the rear of the slug. Co-injection of a specific inhibitor of the cAR1 serpentine cAMP receptor almost completely prevents the cAMP-induced nuclear translocation, showing that most or all of the cAMP signal is transduced by cAR1. Dd-GFP:STATa also rapidly translocates into the nuclei of cells adjoining the front and back cut edges when a slug is bisected. Less severe mechanical disturbances, such as pricking the rear of a slug with an unfilled micropipette, also cause a more limited nuclear translocation of Dd-GFP:STATa. We propose that these signalling events form part of a repair mechanism that is activated when the migrating slug suffers mechanical damage.
Movies available on-line: http://www.personal.dundee.ac.uk/∼cjweijer/STATa_GFP.htm and http://www.biologists.com/Development/movies/dev3344.html
An instructive function for Notch in promoting gliogenesis in the zebrafish retina
Authors: Scheer Nico , Groth Anne , Hans Stefan , A. Campos-Ortega José 
Published: April 2021

ABSTRACT
The Gal4-UAS technique has been used to misexpress a constitutively active Notch receptor variant (notch1a-intra) in the developing zebrafish retina. This is the first study to use this technique to misexpress genes and assess their function in neural development of the zebrafish. Expression of activated Notch1a either ubiquitously, driven by a heat- shock70 promoter, or in a spatially regulated manner, controlled by the deltaD promoter, causes a block in neuronal differentiation that affects all cell types. Developing cells take on either a glial fate or remain undifferentiated. A large number of cells eventually undergo apoptosis. These phenotypic effects of activated Notch1a are expressed cell autonomously. Cells within central regions of the retina adopt a glial fate if they express activated Notch1a in a time window that extends from 27 to 48 hours postfertilization. This period corresponds mainly to the time of origin of ganglion cells in the normal retina. Activation of notch1a at later stages results in defects in cell type specification that remain restricted to the ciliary marginal zone, whereas neuronal types are specified normally within the central region. These observations indicate that glial differentiation is initiated by Notch1a-intra expressing cells, which become postmitotic in the same time window. Our results strongly suggest that Notch1a instructs a certain cell population to enter gliogenesis, and keeps the remaining cells in an undifferentiated state. Some or all of these cells will eventually succumb to apoptosis.
Regulation of imprinted X-chromosome inactivation in mice by Tsix
Authors: Sado Takashi , Wang Zhenjuan , Sasaki Hiroyuki , Li En 
Published: April 2021

ABSTRACT
In mammals, X-chromosome inactivation is imprinted in the extra-embryonic lineages with paternal X chromosome being preferentially inactivated. In this study, we investigate the role of Tsix, the antisense transcript from the Xist locus, in regulation of Xist expression and X- inactivation. We show that Tsix is transcribed from two putative promoters and its transcripts are processed. Expression of Tsix is first detected in blastocysts and is imprinted with only the maternal allele transcribed. The imprinted expression of Tsix persists in the extra- embryonic tissues after implantation, but is erased in embryonic tissues. To investigate the function of Tsix in X- inactivation, we disrupted Tsix by insertion of an IRESβgeo cassette in the second exon, which blocked transcripts from both promoters. While disruption of the paternal Tsix allele has no adverse effects on embryonic development, inheritance of a disrupted maternal allele results in ectopic Xist expression and early embryonic lethality, owing to inactivation of both X chromosomes in females and single X chromosome in males. Further, early developmental defects of female embryos with maternal transmission of Tsix mutation can be rescued by paternal inheritance of the Xist deletion. These results provide genetic evidence that Tsix plays a crucial role in maintaining Xist silencing in cis and in regulation of imprinted X-inactivation in the extra- embryonic tissues.
Analysis of RNA associated with P granules in germ cells of C. elegans adults
Authors: A. Schisa Jennifer , N. Pitt Jason , R.Priess James 
Published: April 2021

ABSTRACT
P granules are cytoplasmic structures of unknown function that are associated with germ nuclei in the C. elegans gonad, and are localized exclusively to germ cells, or germ cell precursors, throughout the life cycle. All the known protein components of P granules contain putative RNA- binding motifs, suggesting that RNA is involved in either the structure or function of the granules. However, no specific mRNAs have been identified within P granules in the gonad. We show here that P granules normally contain a low level of RNA, and describe conditions that increase this level. We present evidence that several, diverse mRNAs, including pos-1, mex-1, par-3, skn-1, nos-2 and gld- 1 mRNA, are present at least transiently within P granules.
In contrast, actin and tubulin mRNA and rRNA are either not present in P granules, or are present at relatively low levels. We show that pgl-1 and the glh (Vasa-related) gene family, which encode protein components of P granules, do not appear essential for RNA to concentrate in P granules; these proteins may instead function in events that are a prerequisite for RNAs to be transported efficiently from the nuclear surface.
Meis3 synergizes with Pbx4 and Hoxb1b in promoting hindbrain fates in the zebrafish
Authors: Vlachakis Nikolaos , Choe Seong-Kyu , Sagerström Charles 
Published: April 2021

ABSTRACT
Many Hox proteins are thought to require Pbx and Meis co-factors to specify cell identity during embryogenesis. Here we demonstrate that Meis3 synergizes with Pbx4 and Hoxb1b in promoting hindbrain fates in the zebrafish. We find that Hoxb1b and Pbx4 act together to induce ectopic hoxb1a expression in rhombomere 2 of the hindbrain. In contrast, Hoxb1b and Pbx4 acting together with Meis3 induce hoxb1a, hoxb2, krox20 and valentino expression rostrally and cause extensive transformation of forebrain and midbrain fates to hindbrain fates, including differentiation of excess rhombomere 4-specific Mauthner neurons. This synergistic effect requires that Hoxb1b and Meis3 have intact Pbx-interaction domains, suggesting that their in vivo activity is dependent on binding to Pbx4. In the case of Meis3, binding to Pbx4 is also required for nuclear access. Our results are consistent with Hoxb1b and Meis3 interacting with Pbx4 to form complexes that regulate hindbrain development during zebrafish embryogenesis.
The role of presenilin 1 during somite segmentation
Authors: Koizumi Ken-ichi , Nakajima Mitsunari , Yuasa Shigeki , Saga Yumiko , Sakai Tsuyoshi , Kuriyama Takayuki , Shirasawa Takuji , Koseki Haruhiko 
Published: April 2021

ABSTRACT
The Notch signalling pathway plays essential roles during the specification of the rostral and caudal somite halves and subsequent segmentation of the paraxial mesoderm. We have re-investigated the role of presenilin 1 (Ps1; encoded by Psen1) during segmentation using newly generated alleles of the Psen1 mutation. In Psen1-deficient mice, proteolytic activation of Notch1 was significantly affected and the expression of several genes involved in the Notch signalling pathway was altered, including Delta-like3, Hes5, lunatic fringe (Lfng) and Mesp2. Thus, Ps1-dependent activation of the Notch pathway is essential for caudal half somite development. We observed defects in Notch signalling in both the caudal and rostral region of the presomitic mesoderm. In the caudal presomitic mesoderm, Ps1 was involved in maintaining the amplitude of cyclic activation of the Notch pathway, as represented by significant reduction of Lfng expression in Psen1-deficient mice. In the rostral presomitic mesoderm, rapid downregulation of the Mesp2 expression in the presumptive caudal half somite depends on Ps1 and is a prerequisite for caudal somite half specification. Chimaera analysis between Psen1-deficient and wild-type cells revealed that condensation of the wild-type cells in the caudal half somite was concordant with the formation of segment boundaries, while mutant and wild-type cells intermingled in the presomitic mesoderm. This implies that periodic activation of the Notch pathway in the presomitic mesoderm is still latent to segregate the presumptive rostral and caudal somite. A transient episode of Mesp2 expression might be needed for Notch activation by Ps1 to confer rostral or caudal properties. In summary, we propose that Ps1 is involved in the functional manifestation of the segmentation clock in the presomitic mesoderm.
Nuclear import of activated D-ERK by DIM-7, an importin family member encoded by the gene moleskin
Authors: Lorenzen James A. , Baker Scott E. , Denhez Fabienne , Melnick Michael B. , Brower Danny L. , Perkins Lizabeth A. 
Published: April 2021

ABSTRACT
The initiation of gene expression in response to Drosophila receptor tyrosine kinase signaling requires the nuclear import of the MAP kinase, D-ERK. However, the molecular details of D-ERK translocation are largely unknown. In this regard, we have identified D-Importin-7 (DIM-7), the Drosophila homolog of vertebrate importin 7, and its gene moleskin. DIM-7 exhibits a dynamic nuclear localization pattern that overlaps the spatial and temporal profile of nuclear, activated D-ERK. Co-immunoprecipitation experiments show that DIM-7 associates with phosphorylated D-ERK in Drosophila S2 cells. Furthermore, moleskin mutations enhance hypomorphic and suppress hypermorphic D-ERK mutant phenotypes. Deletion or mutation of moleskin dramatically reduces the nuclear localization of activated D-ERK. Directly linking DIM-7 to its nuclear import, this defect can be rescued by the expression of wild-type DIM-7. Mutations in the Drosophila Importin β homolog Ketel, also reduce the nuclear localization of activated D-ERK. Together, these data indicate that DIM-7 and Ketel are components of the nuclear import machinery for activated D-ERK.
The winged-helix transcription factor FoxD3 is important for establishing the neural crest lineage and repressing melanogenesis in avian embryos
Authors: Kos Robert , Reedy Mark V. , Johnson Randy L. , Erickson Carol A. 
Published: April 2021

Abstract
The winged-helix or forkhead class of transcription factors has been shown to play important roles in cell specification and lineage segregation. We have cloned the chicken homolog of FoxD3, a member of the winged-helix class of transcription factors, and analyzed its expression. Based on its expression in the dorsal neural tube and in all neural crest lineages except the late-emigrating melanoblasts, we predicted that FoxD3 might be important in the segregation of the neural crest lineage from the neural epithelium, and for repressing melanogenesis in early-migrating neural crest cells.
Misexpression of FoxD3 by electroporation in the lateral neural epithelium early in neural crest development produced an expansion of HNK1 immunoreactivity throughout the neural epithelium, although these cells did not undergo an epithelial/mesenchymal transformation. To test whether FoxD3 represses melanogenesis in early migrating neural crest cells, we knocked down expression in cultured neural crest with antisense oligonucleotides and in vivo by treatment with morpholino antisense oligonucleotides. Both experimental approaches resulted in an expansion of the melanoblast lineage, probably at the expense of neuronal and glial lineages. Conversely, persistent expression of FoxD3 in late-migrating neural crest cells using RCAS viruses resulted in the failure of melanoblasts to develop.
We suggest that FoxD3 plays two important roles in neural crest development. First, it is involved in the segregation of the neural crest lineage from the neuroepithelium. Second, it represses melanogenesis, thereby allowing other neural crest derivatives to differentiate during the early stages of neural crest patterning.
The HCL gene of Medicago truncatula controls Rhizobium-induced root hair curling
Authors: Catoira Romy , Timmers Antonius C. J. , Maillet Fabienne , Galera Christine , Penmetsa R. Varma , Cook ouglas , Dénarié Jean , Gough Clare 
Published: April 2021

ABSTRACT
The symbiotic infection of the model legume Medicago truncatula by Sinorhizobium meliloti involves marked root hair curling, a stage where entrapment of the microsymbiont occurs in a chamber from which infection thread formation is initiated within the root hair. We have genetically dissected these early symbiotic interactions using both plant and rhizobial mutants and have identified a M. truncatula gene, HCL, which controls root hair curling. S. meliloti Nod factors, which are required for the infection process, induced wild-type epidermal nodulin gene expression and root hair deformation in hcl mutants, while Nod factor induction of cortical cell division foci was reduced compared to wild-type plants. Studies of the position of nuclei and of the microtubule cytoskeleton network of hcl mutants revealed that root hair, as well as cortical cells, were activated in response to S. meliloti. However, the asymmetric microtubule network that is typical of curled root hairs, did not form in the mutants, and activated cortical cells did not become polarised and did not exhibit the microtubular cytoplasmic bridges characteristic of the pre-infection threads induced by rhizobia in M. truncatula. These data suggest that hcl mutations alter the formation of signalling centres that normally provide positional information for the reorganisation of the microtubular cytoskeleton in epidermal and cortical cells.
A novel role for VEGF in endocardial cushion formation and its potential contribution to congenital heart defects
Authors: Dor Yuval , Camenisch Todd D. , Itin Ahuva , Fishman Glenn I. , McDonald John A. , Carmeliet Peter , Keshet Eli 
Published: April 2021

ABSTRACTNormal cardiovascular development is exquisitely dependent on the correct dosage of the angiogenic growth factor and vascular morphogen vascular endothelial growth factor (VEGF). However, cardiac expression of VEGF is also robustly augmented during hypoxic insults, potentially mediating the well-established teratogenic effects of hypoxia on heart development. We report that during normal heart morphogenesis VEGF is specifically upregulated in the atrioventricular (AV) field of the heart tube soon after the onset of endocardial cushion formation (i.e. the endocardium-derived structures that build the heart septa and valves). To model hypoxia-dependent induction of VEGF in vivo, we conditionally induced VEGF expression in the myocardium using a tetracycline-regulated transgenic system. Premature induction of myocardial VEGF in E9.5 embryos to levels comparable with those induced by hypoxia prevented formation of endocardial cushions. When added to explanted embryonic AV tissue, VEGF fully inhibited endocardial-to-mesenchymal transformation. Transformation was also abrogated in AV explants subjected to experimental hypoxia but fully restored in the presence of an inhibitory soluble VEGF receptor 1 chimeric protein. Together, these results suggest a novel developmental role for VEGF as a negative regulator of endocardial-to-mesenchymal transformation that underlies the formation of endocardial cushions. Moreover, ischemia-induced VEGF may be the molecular link between hypoxia and congenital defects in heart septation.
The Drosophila sex determination hierarchy modulates wingless and decapentaplegic signaling to deploy dachshund sex-specifically in the genital imaginal disc
Authors: Keisman Eric L. , Baker Bruce S. 
Published: April 2021

ABSTRACT
The integration of multiple developmental cues is crucial to the combinatorial strategies for cell specification that underlie metazoan development. In the Drosophila genital imaginal disc, which gives rise to the sexually dimorphic genitalia and analia, sexual identity must be integrated with positional cues, in order to direct the appropriate sexually dimorphic developmental program. Sex determination in Drosophila is controlled by a hierarchy of regulatory genes. The last known gene in the somatic branch of this hierarchy is the transcription factor doublesex (dsx); however, targets of the hierarchy that play a role in sexually dimorphic development have remained elusive. We show that the gene dachshund (dac) is differentially expressed in the male and female genital discs, and plays sex-specific roles in the development of the genitalia. Furthermore, the sex determination hierarchy mediates this sex-specific deployment of dac by modulating the regulation of dac by the pattern formation genes wingless (wg) and decapentaplegic (dpp). We find that the sex determination pathway acts cell-autonomously to determine whether dac is activated by wg signaling, as in females, or by dpp signaling, as in males.
An experimental approach to the development of the ear capsule in the turtle, Chelydra serpentina
Authors: Toerien M. J. 
Published: April 2021

ABSTRACT
With the exception of part of the floor which is of basal plate origin, the cartilaginous ear capsule is absent following complete extirpation of the otocyst at the 12-20 somite stages. Cartilaginous structures occupying the metotic fissure are similarly absent. A metotic cartilage is present in Chelonia and develops independently of the ear capsule. The full development of the stapes footplate is inhibited by the absence of the ear capsule.
The energetics of cleavage in Planorbis exustus
Authors: Sherbet Gajanan V. , Lakshmi M. S. 
Published: April 2021

ABSTRACT
The effect of sodium azide on the processes of cleavage in Planorbis exustus has been studied. The phase of cleavage division at which treatment is begun and the delay caused in subsequent divisions have a definite relationship to each other. The delay caused by azide, after it becomes apparent, does not progressively increase but is maintained. The results are discussed from the point of view of the energy mechanism involved. A reservoir system, probably of phosphorylated compounds, seems to operate. When carbohydrate metabolism is selectively inhibited at some point in the Embden-Meyerhof pathway, the embryos seem to be capable of metabolizing fats for the purposes of deriving energy for the cleavage processes.
An experimental approach to the problem of the derivation of the vaginal epithelium
Authors: Forsberg John-Gunnar 
Published: April 2021

ABSTRACT
In earlier papers the present author (Forsberg, 1963, 1965a, b;Forsberg & Olivecrona, 1964) has presented studies of the derivation and differentiation of the vaginal epithelium by morphological, histochemical and autoradiographic methods and by counts of mitotic rates. These investigations favour the view that the vaginal epithelium in mouse and rat has a dual origin: the anterior part being derived from the Müllerian epithelium and the posterior part from the sinus epithelium. This means that in these species the pseudostratified columnar Müllerian epithelium in the vaginal region undergoes a transformation into a stratified squamous epithelium. The possible mechanism behind this transformation has been discussed (Forsberg & Olivecrona, 1965). Results from estradiol treatment of neonatal mice during the differentiation of the vaginal epithelium support the above-mentioned investigations. (For a detailed review on the problem of the derivation of the vaginal epithelium, see Forsberg, 1963.)
Further studies of the effects of deprivation of sulfate on the early development of the sea urchin Paracentrotus lividus
Authors: Immers J. , Runnström J. 
Published: April 2021

ABSTRACT
The morphological effects of sulfate-free medium on sea urchin embryos were described in detail by Herbst (1904). Further studies were carried out by Lindahl (1936,1942). He was the first to consider metabolic aspects of the rôle of sulfate in the development of the sea urchin. Immers (1956, 1959, 1961a and b, 1962) studied the distribution and function of acid mucopolysaccharides in early developmental stages of sea urchins, mainly Paracentrotus lividus. A dominant group of these acid polysaccharides are sulfated. Their location in the blastocoel, in the hyaline layer and in the lumen of the intestine could be demonstrated by staining of sectioned specimens with the ferri-acetic reagent of Hale (1946). In blastulae or gastrulae raised in sulfate-free sea water these regions are negative with respect to Hale staining (Immers, 1961b). On the other hand, the ectodermal nuclei of the animal region of the embryos are stained with the Hale reagent although the nuclei of the vegetal region remained unstained (l.c.).