bluuebunny/crossref_metadata_2025_split huggingface dataset:
Slug, a zinc finger gene previously implicated in the early patterning of the mesoderm and the neural crest, is also involved in chick limb development
Authors: Ros Maria A. , Sefton Mark , Nieto M. Angela 
Published: April 2021

Summary
The great advances made over the last few years in the identification of signalling molecules that pattern the limb bud along the three axes make the limb an excellent model system with which to study developmental mechanisms in vertebrates. The understanding of the signalling networks and their mutual interactions during limb development requires the characterisation of the corresponding downstream genes. In this study we report the expression pattern of Slug, a zinc-finger-containing gene of the snail family, during the development of the limb, and its regulation by distinct axial signalling systems. Slug expression is highly dynamic, and at different stages of limb development can be correlated with the zone of polarizing activity, the progress zone and the interdigital areas. We show that the maintenance of its expression is dependent on signals from the apical ectodermal ridge and independent of Sonic Hedgehog. We also report that, in the interdigit, apoptotic cells lie outside of the domains of Slug expression. The correlation of Slug expression with areas of undifferentiated mesenchyme at stages of tissue differentiation is consistent with its role in early development, in maintaining the mesenchymal phenotype and repressing differentiation processes. We suggest that Slug is involved in the epithelial- mesenchymal interactions that lead to the maintenance of the progress zone.
A molecular basis for transdetermination in Drosophila imaginal discs: interactions between wingless and decapentaplegic signaling
Authors: Maves Lisa , Schubiger Gerold 
Published: April 2021

ABSTRACT
We are investigating how Drosophila imaginal disc cells establish and maintain their appendage-specific determined states. We have previously shown that ectopic expression of wingless (wg) induces leg disc cells to activate expression of the wing marker Vestigial (Vg) and transdetermine to wing cells. Here we show that ectopic wg expression non-cell-autonomously induces Vg expression in leg discs and that activated Armadillo, a cytosolic transducer of the Wg signal, cell-autonomously induces Vg expression in leg discs, indicating that this Vg expression is directly activated by Wg signaling. We find that ubiquitous expression of wg in leg discs can induce only dorsal leg disc cells to express Vg and transdetermine to wing. Dorsal leg disc cells normally express high levels of decapentaplegic (dpp) and its downstream target, optomotor-blind (omb). We find that high levels of dpp expression, which are both necessary and sufficient for dorsal leg development, are required for wg-induced transdetermination. We show that dorsalization of ventral leg disc cells, through targeted expression of either dpp or omb, is sufficient to allow wg to induce Vg expression and wing fate. Thus, dpp and omb promote both dorsal leg cell fate as well as transdetermination-competent leg disc cells. Taken together, our results show that the Wg and Dpp signaling pathways cooperate to induce Vg expression and leg-to-wing transdetermination. We also show that a specific vg regulatory element, the vg boundary enhancer, is required for transdetermination. We propose that an interaction between Wg and Dpp signaling can explain why leg disc cells transdetermine to wing and that our results have implications for normal leg and wing development.
Nkx5-1 controls semicircular canal formation in the mouse inner ear
Authors: Hadrys Thorsten , Braun Thomas , Rinkwitz-Brandt Silke , Arnold Hans-Henning , Bober Eva 
Published: April 2021

ABSTRACT
The inner ear develops from the otic vesicle, a one-cell-thick epithelium, which eventually transforms into highly complex structures including the sensory organs for balance (vestibulum) and hearing (cochlea). Several mouse inner ear mutations with hearing and balance defects have been described but for most the underlying genes have not been identified, for example, the genes controlling the development of the vestibular organs. Here, we report the inactivation of the homeobox gene, Nkx5-1, by homologous recombination in mice. This gene is expressed in vestibular structures throughout inner ear development. Mice carrying the Nkx5-1 null mutation exhibit behavioural abnormalities that resemble the typical hyperactivity and circling movements of the shaker/waltzer type mutants. The balance defect correlates with severe malformations of the vestibular organ in Nkx5-1−/− mutants, which fail to develop the semicircular canals. Nkx5-1 is the first ear-specific molecule identified to play a crucial role in the formation of the mammalian vestibular system.
The paternal allele of the H19 gene is progressively silenced during early mouse development: the acetylation status of histones may be involved in the generation of variegated expression patterns
Authors: Svensson Kristian , Mattsson Ragnar , James Tharappel C. , Wentzel Parri , Pilartz Marcel , MacLaughlin John , Miller Stephen J. , Olsson Tim , Eriksson Ulf J. , Ohlsson Rolf 
Published: April 2021

ABSTRACT
Transcriptional silencing can reflect heritable, epigenetic inactivation of genes, either singly or in groups, during the life-time of an organism. This phenomenon is exemplified by parent-of-origin-specific inactivation events (genomic imprinting) for a subset of mammalian autosomal genes, such as H19. Very little is known, however, about the timing and mechanism(s) of silencing of the paternal H19 allele during mouse development. Using a novel in situ approach, we present evidence that the silencing of the paternal H19 allele is progressive in the trophectodermal lineage during early mouse development and generates variegated expression patterns. The silencing process apparently involves recruitment of histone deacetylases since the mosaic paternal-specific H19 expression reappears in trichostatin A-treated mouse conceptuses, undergoing in vitro organogenesis. Moreover, the paternal H19 alleles of PatDup.d7 placentas, in which a region encompassing the H19 locus of chromosome 7 is bipaternally derived, partially escape the silencing process and are expressed in a variegated manner. We suggest that allele-specific silencing of H19 share some common features with chromatin-mediated silencing in position-effect variegation.
Genetic regulation of entry into meiosis in Caenorhabditis elegans
Authors: Kadyk Lisa C. , Kimble Judith 
Published: April 2021

ABSTRACT
The Caenorhabditis elegans germline is composed of mitotically dividing cells at the distal end that give rise to meiotic cells more proximally. Specification of the distal region as mitotic relies on induction by the somatic distal tip cell and the glp-1 signal transduction pathway. However, the genetic control over the transition from mitosis to meiosis is not understood. In this paper, we report the identification of a gene, gld-2, that has at least two functions in germline development. First, gld-2 is required for normal progression through meiotic prophase. Second, gld-2 promotes entry into meiosis from the mitotic cell cycle. With respect to this second function, gld-2 appears to be functionally redundant with a previously described gene, gld-1 (Francis, R., Barton, M. K., Kimble, J. and Schedl, T. (1995) Genetics 139, 579-606). Germ cells in gld-1(ø) and gld-2 single mutants enter meiosis at the normal time, but germ cells in gld-2 gld-1(ø) double mutants do not enter meiosis. Instead, the double mutant germline is mitotic throughout and forms a large tumor. We suggest that gld-1 and gld-2 define two independent regulatory pathways, each of which can be sufficient for entry into meiosis. Epistasis analyses show that gld-1 and gld-2 work downstream of the glp-1 signal transduction pathway. Therefore, we hypothesize that glp-1 promotes proliferation by inhibiting the meiosis-promoting functions of gld-1 and gld-2.
The Tlx-2 homeobox gene is a downstream target of BMP signalling and is required for mouse mesoderm development
Authors: Tang Shao Jun , Hoodless Pamela A. , Lu Zhan , Breitman Martin L. , McInnes Roderick R. , Wrana Jeffrey L. , Buchwald Manuel 
Published: April 2021

ABSTRACT
TGFβ-related factors are critical regulators of vertebrate mesoderm development. However, the signalling cascades required for their function during this developmental process are poorly defined. Tlx-2 is a homeobox gene expressed in the primitive streak of mouse embryos. Exogenous BMP-2 rapidly activates Tlx-2 expression in the epiblast of E6.5 embryos. A Tlx-2 promoter element responds to BMP-2 signals in P19 cells, and this response is mediated by BMP type I receptors and Smad1. These results suggest that Tlx-2 is a downstream target gene for BMP signalling in the primitive streak where BMP-4 and other TGFβ-related factors are expressed. Furthermore, disruption of Tlx-2 function leads to early embryonic lethality. Similar to BMP4 and ALK3 mutants, the mutant embryos display severe defects in primitive streak and mesoderm formation. These experiments thus define a BMP/Tlx-2 signalling pathway that is required during early mammalian gastrulation.
Selective disruption of neuregulin-1 function in vertebrate embryos using ribozyme-tRNA transgenes
Authors: Zhao Jack Jiagang , Lemke Greg 
Published: April 2021

ABSTRACT
The products of the neuregulin-1 gene constitute a set of polypeptide growth factors whose signalling through the ErbB receptors is essential to the growth and differentiation of many cell types in culture. Although studies with neuregulin-1 mutant mice have demonstrated that these growth factors are also essential regulators of cellular differentiation in vivo, the mid-embryonic death of these mutants precludes an analysis of hypothesized neuregulin-1 roles in later aspects of development. To circumvent this early lethality, we have pursued a ribozyme-based strategy for the perturbation of neuregulin-1 function in developing chick embryos. Early administration of a retrovirus carrying neuregulin-1 hammerhead-type ribozymes to blastoderm-stage embryos leads to an embryonic lethal phenotype that results from the failure of ventricular trabeculation in the developing heart, a faithful phenocopy of the mouse neuregulin-1 mutations. Later, more localized delivery of the ribozyme to the developing retina inhibits both the differentiation of retinal ganglion cell neurons and the proliferation of the neuroepithelial cells from which they derive. These results suggest that neuregulin-1 promotes both muscle cell differentiation in the heart and neuronal differentiation in the central nervous system. In addition, they demonstrate the utility of hammerhead ribozymes as a simple, effective and easily adaptable method of conditional gene inactivation in vertebrates.
Ventricular muscle-restricted targeting of the RXRα gene reveals a non-cell-autonomous requirement in cardiac chamber morphogenesis
Authors: Chen Ju , Kubalak Steven W. , Chien Kenneth R. 
Published: April 2021

ABSTRACT
Mouse embryos lacking the retinoic acid receptor gene RXRα die in midgestation from hypoplastic development of the myocardium of the ventricular chambers and consequent cardiac failure. In this study, we address the issue of whether the RXRα gene is required in the cardiomyocyte lineage by generating mice that harbor a ventricular restricted deficiency in RXRα at the earliest stages of ventricular chamber specification. We first created a conditional (‘floxed’) allele of RXRα by flanking a required exon of the gene with loxP recombination sequences. To achieve ventricular myocardium-specific gene targeting, and to avoid potential transgenic artifacts, we employed a knock-in strategy to place cre recombinase coding sequences into the myosin light chain 2v (MLC2v) genomic locus, a gene which in the heart is expressed exclusively in ventricular cardiomyocytes at the earliest stages of ventricular specification. Crossing the MLC2v-cre allele with the floxed RXRα gene resulted in embryos in which approximately 80% of the ventricular cardiomyocytes lacked RXRα function, and yet which displayed a completely normal phenotype, without evidence of the wide spectrum of congenital heart disease phenotype seen in RXRa−/−embryos, and normal adult viability. We conclude that the RXRα mutant phenotype is not cell autonomous for the cardiomyocyte lineage, and suggest that RXRα functions in a neighboring compartment of the developing heart to generate a signal that is required for ventricular cardiomyocyte development and chamber maturation.
Position dependent control of cell fate in the Fucus embryo: role of intercellular communication
Authors: François-Yves Bouget , Berger Frédéric , Brownlee Colin 
Published: April 2021

ABSTRACT
The early embryo of the brown alga Fucus comprises two cell types, i.e. rhizoid and thallus which are morphogically and cytologically distinguishable. Previous work has pointed to the cell wall as a source of position-dependent information required for polarisation and fate determination in the zygote and 2-celled embryo. In this study we have analysed the mechanism(s) of cell fate control and pattern formation at later embryonic stages using a combination of laser microsurgery and microinjection. The results indicate that the cell wall is required for maintenance of pre-existing polarity in isolated intact cells. However, all cell types ultimately have the capacity to re-differentiate or regenerate rhizoid cells in response to ablation of neighbouring cells. This regeneration is regulated in a position-dependent manner and is strongly influenced by intercellular communication, probably involving transport or diffusion of inhibitory signals which appear to be essential for regulation of cell fate decisions. This type of cell-to-cell communication does not involve symplastic transport or direct cell-cell contact inhibition. Apoplastic diffusible gradients appear to be involved in pattern formation in the multicellular embryo.
Sonic hedgehog is required for survival of both myogenic and chondrogenic somitic lineages
Authors: Teillet M.-A. , Watanabe Y. , Jeffs P. , Duprez D. , Lapointe F. , Le Douarin N. M. 
Published: April 2021

ABSTRACT
In vertebrates, the medial moieties of the somites give rise to the vertebrae and epaxial muscles, which develop in close relationship with the axial organs, neural tube and notochord. The lateral moieties contribute to the ribs and to limb and body wall muscles (hypaxial muscles) after a phase of lateral and ventral migration. Surgical ablation of the neural tube and notochord in the chick embryo during segmentation and early differentiation of the somites (day 2 of incubation) does not affect primary development of the hypaxial muscles, but leads to a complete absence of epaxial muscles, vertebrae and ribs, due to cell death in the somites. Here we demonstrate that cell death, which occurs within 24 hours of excision of the axial organs, affects both myogenic and chondrogenic cell lineages defined, respectively, by the expression of MyoD and Pax-1 genes. In contrast, Pax-3 transcripts, normally present in cells giving rise to hypaxial muscles, are preserved in the excised embryos. Backgrafting either the ventral neural tube or the notochord allows survival of MyoD- and Pax-1-expressing cells. Similarly, Sonic hedgehog-producing cells grafted in place of axial organs also rescue MyoD- and Pax-1-expressing cells from death and allow epaxial muscles, ribs and vertebrae to undergo organogenesis. These results demonstrate that the ventral neural tube and the notochord promote the survival of both myogenic and chondrogenic cell lineages in the somites and that this action is mediated by Sonic hedgehog.
Thylacine 1 is expressed segmentally within the paraxial mesoderm of the Xenopus embryo and interacts with the Notch pathway
Authors: Sparrow Duncan B. , Jen Wui-Chuong , Kotecha Surendra , Towers Norma , Kintner Chris , Mohun Timothy J. 
Published: April 2021

ABSTRACT
The presomitic mesoderm of vertebrates undergoes a process of segmentation in which cell-cell interactions mediated by the Notch family of receptors and their associated ligands are involved. The vertebrate homologues of Drosophila Delta are expressed in a dynamic, segmental pattern within the presomitic mesoderm, and alterations in the function of these genes leads to a perturbed pattern of somite segmentation. In this study we have characterised Thylacine 1 which encodes a basic helix-loop-helix class transcription activator. Expression of Thylacine is restricted to the presomitic mesoderm, localising to the anterior half of several somitomeres in register with domains of X-Delta-2 expression. Ectopic expression of Thylacine in embryos causes segmentation defects similar to those seen in embryos in which Notch signalling is altered, and these embryos also show severe disruption in the expression patterns of the marker genes X-Delta-2 and X-ESR5 within the presomitic mesoderm. Finally, the expression of Thylacine is altered in embryos when Notch signalling is perturbed. These observations suggest strongly that Thylacine 1 has a role in the segmentation pathway of the Xenopus embryo, by interacting with the Notch signalling pathway.
Dystonin is an essential component of the Schwann cell cytoskeleton at the time of myelination
Authors: Bernier Gilbert , Repentigny Yves De , Mathieu Martine , David Samuel , Kothary Rashmi 
Published: April 2021

ABSTRACT
A central role for the Schwann cell cytoskeleton in the process of peripheral nerve myelination has long been suggested. However, there is no genetic or biological evidence as yet to support this assumption. Here we show that dystonia musculorum (dt) mice, which carry mutations in dystonin, a cytoskeletal crosslinker protein, have hypo/amyelinated peripheral nerves. In neonatal dt mice, Schwann cells were arrested at the promyelinating stage and had multiple myelinating lips. Nerve graft experiments and primary cultures of Schwann cells demonstrated that the myelination abnormality in dt mice was autonomous to Schwann cells. In culture, dt Schwann cells showed abnormal polarization and matrix attachment, and had a disorganized cytoskeleton. Finally, we show that the dt mutation was semi-dominant, heterozygous animals presenting hypo- and hyper-myelinated peripheral nerves. Altogether, our results suggest that dt Schwann cells are deficient for basement membrane interaction and demonstrate that dystonin is an essential component of the Schwann cell cytoskeleton at the time of myelination.
Environmental control of the cell cycle in Drosophila: nutrition activates mitotic and endoreplicative cells by distinct mechanisms
Authors: Britton Jessica S. , Edgar Bruce A. 
Published: April 2021

ABSTRACT
In newly hatched Drosophila larvae, quiescent cells reenter the cell cycle in response to dietary amino acids. To understand this process, we varied larval nutrition and monitored effects on cell cycle initiation and maintenance in the mitotic neuroblasts and imaginal disc cells, as well as the endoreplicating cells in other larval tissues. After cell cycle activation, mitotic and endoreplicating cells respond differently to the withdrawal of nutrition: mitotic cells continue to proliferate in a nutrition-independent manner, while most endoreplicating cells reenter a quiescent state. We also show that ectopic expression of Drosophila Cyclin E or the E2F transcription factor can drive quiescent endoreplicating cells, but not quiescent imaginal neuroblasts, into S-phase. Conversely, we demonstrate that quiescent imaginal neuroblasts, but not quiescent endoreplicating cells, can be induced to enter the cell cycle when co-cultured with larval fat body in vitro. These results demonstrate a fundamental difference in the control of cell cycle activation and maintenance in these two cell types, and imply the existence of a novel mitogen generated by the larval fat body in response to nutrition.
pha-4 is Ce-fkh-1, a fork head/HNF-3α,β,γ homolog that functions in organogenesis of the C. elegans pharynx
Authors: Kalb John M. , Lau Karen K. , Goszczynski B. , Fukushige Tetsunari , Moons David , Okkema Peter G. , McGhee James D. 
Published: April 2021

ABSTRACT
The C. elegans Ce-fkh-1 gene has been cloned on the basis of its sequence similarity to the winged-helix DNA binding domain of the Drosophila fork head and mammalian HNF-3α,β,γ genes, and mutations in the zygotically active pha-4 gene have been shown to block formation of the pharynx (and rectum) at an early stage in embryogenesis. In the present paper, we show that Ce-fkh-1 and pha-4 are the same gene. We show that PHA-4 protein is present in nuclei of essentially all pharyngeal cells, of all five cell types. PHA-4 protein first appears close to the point at which a cell lineage will produce only pharyngeal cells, independently of cell type. We show that PHA-4 binds directly to a ‘pan-pharyngeal enhancer element’ previously identified in the promoter of the pharyngeal myosin myo-2 gene; in transgenic embryos, ectopic PHA-4 activates ectopic myo-2 expression. We also show that ectopic PHA-4 can activate ectopic expression of the ceh-22 gene, a pharyngeal-specific NK-2-type homeodomain protein previously shown to bind a muscle-specific enhancer near the PHA-4 binding site in the myo-2 promoter. We propose that it is the combination of pha-4 and regulatory molecules such as ceh-22 that produces the specific gene expression patterns during pharynx development. Overall, pha-4 can be described as an ‘organ identity factor’, completely necessary for organ formation, present in all cells of the organ from the earliest stages, capable of integrating upstream developmental pathways (in this case, the two distinct pathways that produce the anterior and posterior pharynx) and participating directly in the transcriptional regulation of organ specific genes.
Finally, we note that the distribution of PHA-4 protein in C. elegans embryos is remarkably similar to the distribution of the fork head protein in Drosophila embryos: high levels in the foregut/pharynx and hindgut/rectum; low levels in the gut proper. Moreover, we show that pha-4 expression in the C. elegans gut is regulated by elt-2, a C. elegans gut-specific GATA-factor and possible homolog of the Drosophila gene serpent, which influences fork head expression in the fly gut. Overall, our results provide evidence for a highly conserved pathway regulating formation of the digestive tract in all (triploblastic) metazoa.
Eyeless initiates the expression of both sine oculis and eyes absent during Drosophila compound eye development
Authors: Halder Georg , Callaerts Patrick , Flister Susanne , Walldorf Uwe , Kloter Urs , Gehring Walter J. 
Published: April 2021

ABSTRACT
The Drosophila Pax-6 gene eyeless acts high up in the genetic hierarchy involved in compound eye development and can direct the formation of extra eyes in ectopic locations. Here we identify sine oculis and eyes absent as two mediators of the eye-inducing activity of eyeless. We show that eyeless induces and requires the expression of both genes independently during extra eye development. During normal eye development, eyeless is expressed earlier than and is required for the expression of sine oculis and eyes absent, but not vice versa. Based on the results presented here and those of others, we propose a model in which eyeless induces the initial expression of both sine oculis and eyes absent in the eye disc. sine oculis and eyes absent then appear to participate in a positive feedback loop that regulates the expression of all three genes. In contrast to the regulatory interactions that occur in the developing eye disc, we also show that in the embryonic head, sine oculis acts in parallel to eyeless and twin of eyeless, a second Pax-6 gene from Drosophila. Recent studies in vertebrate systems indicate that the epistatic relationships among the corresponding vertebrate homologs are very similar to those observed in Drosophila.