bluuebunny/crossref_metadata_2025_split huggingface dataset:
Distinct subpopulations of enteric neuronal progenitors defined by time of development, sympathoadrenal lineage markers and Mash-1-dependence
Authors: Blaugrund E. , Pham T. D. , Tennyson V. M. , Lo L. , Sommer L. , Anderson D.J. , Gershon M.D. 
Published: April 2021

ABSTRACT
Enteric and sympathetic neurons have previously been proposed to be lineally related. We present independent lines of evidence that suggest that enteric neurons arise from at least two lineages, only one of which expresses markers in common with sympathoadrenal cells. In the rat, sympathoadrenal markers are expressed, in the same order as in sympathetic neurons, by a subset of enteric neuronal precursors, which also transiently express tyrosine hydroxylase. If this precursor pool is eliminated in vitro by complement-mediated lysis, enteric neurons continue to develop; however, none of these are serotonergic. In the mouse, the Mash-1−/− mutation, which eliminates sympathetic neurons, also prevents the development of enteric serotonergic neurons. Other enteric neuronal populations, however, including those that contain calcitonin gene related peptide are present. Enteric tyrosine hydroxylasecontaining cells co-express Mash-1 and are eliminated by the Mash-1−/− mutation, consistent with the idea that in the mouse, as in the rat, these precursors generate serotonergic neurons. Serotonergic neurons are generated early in development, while calcitonin gene related peptide-containing enteric neurons are generated much later. These data suggest that enteric neurons are derived from at least two progenitor lineages. One transiently expresses sympathoadrenal markers, is Mash-1-dependent, and generates early-born enteric neurons, some of which are serotonergic. The other is Mash-1-independent, does not express sympathoadrenal markers, and generates late-born enteric neurons, some of which contain calcitonin gene related peptide.
ERECT WING, the Drosophila member of a family of DNA binding proteins is required in imaginal myoblasts for flight muscle development
Authors: DeSimone Susan , Coelho Carmen , Roy Sudipto , VijayRaghavan K. , White Kalpana 
Published: April 2021

ABSTRACT
The erect wing locus of the fruit fly Drosophila melanogaster encodes a protein, EWG, that shares extensive homology with the P3A2 DNA binding protein of sea urchin and a recently identified mammalian transcription factor. Loss-of-function erect wing alleles result in embryonic lethality. Viable alleles of erect wing cause severe abnormalities of the indirect flight muscles. We have analyzed the spatial pattern of erect wing expression in the developing indirect flight muscles during postembryonic development. EWG is detected, 10 hours after puparium formation, in myoblasts that will form the indirect flight muscles. The early events of muscle development are normal in ewg mutants. However, a few hours after the onset of erect wing expression in myoblasts, defects are seen in the developing indirect flight muscles which subsequently degenerate. We present results that show that the normal development of the indirect flight muscles requires erect wing expression in the progenitor myoblasts themselves. Finally, we examine the role of target muscles in the arborization of motor axons by studying the developing innervation to the flight muscle in erect wing mutants. Our study demonstrates, for the first time, a role for a regulatory gene expressed in imaginal myoblasts in Drosophila.
Spatial and temporal information processing in the sea urchin embryo: modular and intramodular organization of the CyIIIa gene cis-regulatory system
Authors: Kirchhamer Carmen V. , Davidson Eric H. 
Published: April 2021

ABSTRACT
The CyIIIa cytoskeletal actin gene of Strongylocentrotus purpuratus is expressed specifically in the aboral ectoderm. In earlier work we identified a 2.3 kb cis-regulatory region that is necessary and sufficient for correct spatial and temporal expression of a CyIIIa•CAT gene. This region includes about 20 sites of specific protein-DNA interaction, at which at least nine different transcription factors may be bound. All except two of these factors have been cloned. In this work we have analyzed by deletion or mutagenesis each specific interaction. A specific function was identified for every binding site examined. These individual functions include control of amplitude and timing of expression at different phases of embryogenesis, and control of spatial expression. We show that particular negative regulatory interactions are required to repress expression of the CyIIIa•CAT construct in oral ectoderm and in skeletogenic mesenchyme at different stages. In further experiments we determined the overall functional organization of the CyIIIa cis-regulatory system, and we show that this system is modular in its regulatory structure. The ‘proximal module’ (with respect to the transcription start site) extends upstream for about 800 base pairs, and includes nine target sites serviced by six different transcription factors. Its major role is to establish CyIIIa expression in the aboral ectoderm territory as the blastomere founder cells are specified and the oral-aboral axis is determined, and to activate the CyIIIa gene late in cleavage. The ‘middle module,’ which lies upstream of the proximal module, acquires major control of CyIIIa function after the blastula stage. It includes six target sites, serviced by four different factors. The middle module is responsible for a sharp increase in expression occurring during gastrulation, mediated by the positively acting factors that bind within it. The middle module also includes sites at which two different negatively acting spatial control factors bind, the functions of which are required for correct spatial expression late in embryogenesis. The ‘distal module’ contains a number of sites at which a positively acting factor binds, but this module exercises no spatial regula-tory function. Interactions within the distal module are required for the normal levels of function of both the proximal and middle modules.
Maternal β-catenin establishes a ‘dorsal signal’ in early Xenopus embryos
Authors: Wylie C. , Kofron M. , Payne C. , Anderson R. , Hosobuchi M. , Joseph E. , Heasman J. 
Published: April 2021

ABSTRACT
In previous work, we demonstrated that maternally encoded β-catenin, the vertebrate homolog of armadillo, is required for formation of dorsal axial structures in early Xenopus embryos (Heasman, J., Crawford, A., Goldstone, K., Garner-Hamrick, P., Gumbiner, B., Kintner, C., Yoshida-Noro, C. and Wylie, C. (1994). Cell 79, 791-803). Here we investigated, firstly, the role(s) of β-catenin in spatial terms, in different regions of the embryo, by injecting β-catenin mRNA into individual blastomeres of β-catenin-depleted embryos at the 32 cell stage. The results indicate that β-catenin can rescue the dorsal axial structures in a non-cell-autonomous way and without changing the fates of the injected cells. This suggests that cells overexpressing β-catenin send a ‘dorsal signal’ to other cells. This was confirmed by showing that β-catenin overexpressing animal caps did not cause wild-type caps to form mesoderm, but did cause isolated β-catenin-deficient marginal zones to form dorsal mesoderm. Furthermore β-catenin-deficient vegetal masses treated with overexpressing caps regained their ability to act as Nieuwkoop Centers.
Secondly, we studied the temporal activity of β-catenin. We showed that zygotic transcription of β-catenin starts after the midblastula transition (MBT), but does not rescue dorsal axial structures. We further demonstrated that the vegetal mass does not release a dorsal signal until after the onset of transcription, at the midblastula stage, suggesting that maternal β-catenin protein is required at or before this time. Thirdly we investigated where, in relationship to other gene products known to be active in axis formation,β-catenin is placed. We find that BVg1, bFGF, tBR (the truncated form of BMP2/4R), siamois and noggin activities are all downstream of β-catenin, as shown by the fact that injection of their mRNAs rescues the effect of depleting maternally encoded β-catenin. Interference with the action of glycogen synthase kinase (GSK), a vertebrate homolog of the Drosophila gene product, zeste white 3 kinase, does not rescue the effect, suggesting that it is upstream.
Hair matrix germinative epidermal cells confer follicle-inducing capabilities on dermal sheath and high passage papilla cells
Authors: Reynolds Amanda J. , Jahoda Colin A. B. 
Published: April 2021

ABSTRACT
Low passage cultured dermal papilla cells from adult rats stimulate complete hair follicle neogenesis when re-implanted into heterotypic skin. In contrast, cultured sheath cells are non-inductive despite sharing other behav-ioural characteristics (a common lineage and in situ proximity) with papilla cells. However, since sheath cells can behave inductively in amputated follicles after regen-erating the papilla, this poses the question of what influ-ences the sheath to papilla cell transition? During recipro-cal tissue interactions specific epidermal cues are crucial to skin appendage development, and while in vivo assays to date have focussed on dermal interactive influence, our aim was to investigate epidermal potential. We have previously observed that hair follicle epidermal cells display excep-tional interactive behaviour when combined with follicle dermal cells in vitro. Thus in the present study, hair follicle germinative, outer root sheath or skin basal epidermal cells were separately combined with each of three non-inductive dermal cell types (high passage papilla, low passage sheath or fibroblast) and then implanted into small ear skin wounds. The sheath/germinative and papilla/germinative cell implants repeatedly induced giant vibrissa-type follicles and fibres. In complete contrast, any single cell type and all other forms of recombination were consistently non-inductive. Hence, the adult germinative epidermal cells enable non-inductive adult dermal cells to stimulate hair follicle neogenesis, effectively, by altering their ‘status’, causing the sheath cells to ‘specialise’ and the ‘aged’ papilla cells to ‘rejuvenate’.
Mice lacking tartrate-resistant acid phosphatase (Acp 5) have disrupted endochondral ossification and mild osteopetrosis
Authors: Hayman Alison R. , Jones Sheila J. , Boyde Alan , Foster Diane , Colledge William H. , Carlton Mark B. , Evans Martin J. , Cox Timothy M. 
Published: April 2021

ABSTRACT
Mature osteoclasts specifically express the purple, band 5 isozyme (Acp 5) of tartrate-resistant acid phosphatase, a binuclear metalloenzyme that can generate reactive oxygen species. The function of Acp 5 was investigated by targeted disruption of the gene in mice. Animals homozygous for the null Acp 5 allele had progressive foreshortening and deformity of the long bones and axial skeleton but apparently normal tooth eruption and skull plate development, indicating a rôle for Acp 5 in endochondral ossification. Histomorphometry and mineralization density analysis of backscattered electron imaging revealed widened and dis-organized epiphyseal growth plates with delayed mineralization of cartilage in 6- to 8-week-old mutant mice. The membrane bones of the skull showed increased density at all ages examined, indicating defective osteoclastic bone turnover. Increased mineralization density was observed in the long bones of older animals which showed modelling deformities at their extremities: heterozygotes and homozygous Acp 5 mutant mice had tissue that was more mineralized and occupied a greater proportion of the bone in all regions. Thus the findings reflect a mild osteopetrosis due to an intrinsic defect of osteoclastic modelling activity that was confirmed in the resorption pit assay in vitro. We conclude that this bifunctional metalloprotein of the osteoclast is required for normal mineralization of cartilage in developing bones; it also maintains integrity and turnover of the adult skeleton by a critical contribution to bone matrix resorption.
A role for cadherins in tissue formation
Authors: Larue Lionel , Antos Christopher , Butz Stefan , Huber Otmar , Delmas Véronique , Dominis Mara , Kemler Rolf 
Published: April 2021

ABSTRACT
We have produced null mutant mouse embryonic stem cells for the cell adhesion molecule E-cadherin. Such E-cadherin−/− ES cells are defective in cell aggregation; this defect can be corrected by transfection with cDNA for either E-cadherin or N-cadherin driven by a constitutive promoter. The presence (or absence) of E-cadherin regulates the expression of the transcription factor T-brachyury, indicating that cadherins play a role in linking cell surface receptors and gene expression. Comparative analysis of the parental and the genetically altered ES cell lines was performed to examine cell differentiation and the capability to form organized tissues. While differentiating E-cadherin−/− ES cells are still able to express various early and late differentiation markers, they show a clear-cut deficiency in forming organized structures. This phenotype can be rescued by constitutive expression of E-cadherin, which results exclusively in formation of epithelia. In contrast, rescue transfectants expressing N-cadherin show no epithelial structures, instead forming neuroepithelium and cartilage. These results provide the first evidence that specific cadherins directly stimulate differentiation into certain types of tissues.
The Drosophila fish-hook gene encodes a HMG domain protein essential for segmentation and CNS development
Authors: Nambu Patricia A. , Nambu John R. 
Published: April 2021

ABSTRACT
We describe the isolation and analysis of the Drosophila fish-hook (fish) gene, which encodes a novel member of the SOX subgroup of High Mobility Group (HMG) domain proteins that exhibit similarity to the mammalian testis determining factor, SRY. The fish gene is initially expressed in a pair-rule-like pattern which is rapidly replaced by strong neuroectoderm expression. fish null mutants exhibit severe segmentation defects, including loss and/or fusion of abdominal denticle belts and stripe-specific defects in pair-rule and segment polarity gene expression. fish mutant embryos also exhibit loss of specific neurons, fusion of adjacent ventral nerve cord ganglia and aberrant axon scaffold organization. These results indicate an essential role for fish in anterior/posterior pattern formation and nervous system development, and suggest a potential function in modulating the activities of gap and pair-rule proteins.
Patterning the dorsal longitudinal flight muscles (DLM) of Drosophila: insights from the ablation of larval scaffolds
Authors: Fernandes Joyce J. , Keshishian Haig 
Published: April 2021

ABSTRACT
The six Dorsal Longitudinal flight Muscles (DLMs) of Drosophila develop from three larval muscles that persist into metamorphosis and serve as scaffolds for the formation of the adult fibers. We have examined the effect of muscle scaffold ablation on the development of DLMs during metamorphosis. Using markers that are specific to muscle and myoblasts we show that in response to the ablation, myoblasts which would normally fuse with the larval muscle, fuse with each other instead, to generate the adult fibers in the appropriate regions of the thorax. The development of these de novo DLMs is delayed and is reflected in the delayed expression of erect wing, a transcription factor thought to control differentiation events associated with myoblast fusion. The newly arising muscles express the appropriate adult-specific Actin isoform (88F), indicating that they have the correct muscle identity.
However, there are frequent errors in the number of muscle fibers generated. Ablation of the larval scaffolds for the DLMs has revealed an underlying potential of the DLM myoblasts to initiate de novo myogenesis in a manner that resembles the mode of formation of the Dorso-Ventral Muscles, DVMs, which are the other group of indirect flight muscles. Therefore, it appears that the use of larval scaffolds is a superimposition on a commonly used mechanism of myogenesis in Drosophila. Our results show that the role of the persistent larval muscles in muscle patterning involves the partitioning of DLM myoblasts, and in doing so, they regulate formation of the correct number of DLM fibers.
The distal limb environment regulates MyoD accumulation and muscle differentiation in mouse-chick chimæric limbs
Authors: Robson Lesley G. , Hughes Simon M. 
Published: April 2021

ABSTRACT
Differentiation of muscle and cartilage within developing vertebrate limbs occurs in a proximodistal progression. To investigate the cues responsible for regulating muscle pattern, mouse myoblasts were implanted into early chick wings prior to endogenous chick muscle differentiation. Fetal myogenic cells originating from transgenic mice carrying a lacZ reporter were readily detected in vivo after implantation and their state of differentiation determined with species-specific antibodies to MyoD and myosin heavy chain. When mouse myogenic cells are implanted at the growing tip of early stage 21 limbs MyoD expression is suppressed and little differentiation of the mouse cells is detected initially. At later stages ectopically implanted mouse cells come to lie within muscle masses, re-express MyoD and differentiate in parallel with differentiating chick myoblasts. However, if mouse cells are implanted either proximally at stage 21 or into the limb tip at stage 24, situations in which mouse cells encounter endogenous differentiating chick myoblasts earlier, MyoD suppression is not detected and a higher proportion of mouse cells dif- ferentiate. Mouse cells that remain distal to endogenous differentiating myogenic cells are more likely to remain undifferentiated than myoblasts that lie within differenti- ated chick muscle. Undifferentiated distal mouse cells are still capable of differentiating if explanted in vitro, sug- gesting that myoblast differentiation is inhibited in vivo. In vitro, MyoD is suppressed in primary mouse myoblasts by the addition of FGF2 and FGF4 to the culture media. Taken together, our data suggest that the inhibition of myogenic differentiation in the distal limb involves MyoD suppression in myoblasts, possibly through an FGF-like activity.
Genetic evidence for the subdivision of the arthropod limb into coxopodite and telopodite
Authors: González-Crespo Sergio , Morata Ginés 
Published: April 2021

ABSTRACT
Arthropod appendages are thought to have evolved as out-growths from the body wall of a limbless ancestor. Snodgrass, in his Principles of Insect Morphology (1935), proposed that, during evolution, expansion of the body wall would originate the base of the appendages, or coxopodite, upon which the most distal elements that represent the true outer limb, or telopodite, would develop. The homeobox gene Distal-less (Dll), which is required in the Drosophila appendages for development of distal regions, has been proposed to promote formation of telopodite structures above the evolutionary ground-state of non-limb or body wall. Here, we present evidence that another homeobox gene, extradenticle (exd), which is required for appropriate development of the trunk and the proximal parts of the appendages, represents a coxopodite gene. We show that exd function is eliminated from the distal precursors in the developing limb and remains restricted to proximal precursors throughout development. This elimination is important because, when ectopically expressed, exd prevents distal development and gives rise to truncated appendages lacking distal elements. Moreover, the maintenance of exd expression during larval stages, contrary to Dll, does not require the hedgehog (hh) signaling pathway, suggesting that the proximal regions of the appendages develop independently of hh function. Finally, we show that in the crustacean Artemia, exd and Dll are expressed in comparable patterns as in Drosophila, suggesting a conserved genetic mechanism subdividing the arthropod limb.
Expression cloning of a Xenopus T-related gene (Xombi) involved in mesodermal patterning and blastopore lip formation
Authors: Lustig K. D. , Kroll K. L. , Sun E. E. , Kirschner M. W. 
Published: April 2021

ABSTRACT
We have used a functional assay to identify a putative T-box transcription factor (Xombi) that has the ability to induce sites of invagination in the ectoderm of Xenopus embryos that resemble the blastopore lip. Maternal Xombi transcript is first localized to the oocyte’s vegetal cortex and cytoplasm, early sources of mesoderm and endoderm-inducing signals. Soon after zygotic transcription begins, there is a wave of Xombi expression, beginning in dorsal mesoderm and then extending to lateral and ventral mesoderm, that precedes and parallels blastopore lip formation at the border between the mesoderm and endoderm. Transcripts encoding brachyury, Xwnt8 and goosecoid colocalize with Xombi transcripts within the marginal zone; ectopic expression of Xombi induces expression of all three mesodermal genes. In ectodermal explants, Xombi expression is induced by the secreted mesoderm inducers activinA, activinB, Xnr1 and eFGF, and by brachyury, another Xenopus T-box containing gene. The time course and location of Xombi expression, its bio-logical activities and the partial dependence of Xombi expression and blastopore lip formation on fibroblast growth factor (FGF) signaling suggest that Xombi con-tributes to a traveling wave of morphogenesis and differ-entiation during Xenopus gastrulation.
Somatic sex-determining signals act on XX germ cells in Drosophila embryos
Authors: Staab Susanne , Heller Astrid , Steinmann-Zwicky Monica 
Published: April 2021

ABSTRACT
In Drosophila, the enhancer-trap line mgm1 is already specifically expressed in male germ cells. Staining is first detected in 10-hour-old embryos and it is found in later stem cells. This line, which reveals the earliest sex-specific gene expression in the germline known so far, is a useful molecular marker to assess the sexual pathway that germ cells have entered before any overt sexual dimorphism is apparent. XY germ cells that develop in feminized animals express mgm1, which shows that this marker is autonomously expressed in XY germ cells. However, XX germ cells that develop in masculinized animals also express mgm1. Therefore, somatic sex-determining signals have already acted on XX germ cells in 10-hour-old embryos.
Compartments, wingless and engrailed: patterning the ventral epidermis of Drosophila embryos
Authors: Lawrence Peter A. , Sanson Bénédicte , Vincent Jean-Paul 
Published: April 2021

ABSTRACT
Recent experiments on the wing disc of Drosophila have shown that cells at the interface between the anterior and posterior compartments drive pattern formation by becoming the source of a morphogen. Here we ask whether this model applies to the ventral embryonic epidermis. First, we show that interfaces between posterior (engrailed ON) and anterior (engrailed OFF) cells are required for pattern formation. Second, we provide evidence that Wingless could play the role of the morphogen, at least within part of the segmental pattern. We looked at the cuticular structures that develop after different levels of uniform Wingless activity are added back to unsegmented embryos (wingless−engrailed−). Because it is rich in landmarks, the T1 segment is a good region to analyse. There, we find that the cuticle formed depends on the amount of added Wingless activity. For example, a high concentration of Wingless gives the cuticle elements normally found near the top of the presumed gradient.
Unsegmented embryos are much shorter than wild type. If Wingless activity is added in stripes, the embryos are longer than if it is added uniformly. We suggest that the Wingless gradient landscape affects the size of the embryo, so that steep slopes would allow cells to survive and divide, while an even distribution of morphogen would promote cell death. Supporting the hypothesis that Wingless acts as a morphogen, we find that these stripes affect, at a distance, the type of cuticle formed and the planar polarity of the cells.