bluuebunny/crossref_metadata_2025_split huggingface dataset:
Targeted disruption of the low-affinity leukemia inhibitory factor receptor gene causes placental, skeletal, neural and metabolic defects and results in perinatal death
Authors: Ware Carol B. , Horowitz Mark C. , Renshaw Blair R. , Hunt Joan S. , Liggitt Denny , Koblar Simon A. , Gliniak Brian C. , McKenna Hilary J. , Papayannopoulou Thalia , Thoma Bettina , Cheng Linzhao , Donovan Peter J. , Peschon Jacques J. , Bartlett Perry F. , Willis Cynthia R. , Wright Barbara D. , Carpenter Melissa K. , Davison Barry L. , Gearing David P. 
Published: April 2021

ABSTRACT
The low-affinity receptor for leukemia inhibitory factor (LIFR)* interacts with gp130 to induce an intracellular signal cascade. The LIFR-gp130 heterodimer is implicated in the function of diverse systems. Normal placentation is disrupted in LIFR mutant animals, which leads to poor intrauterine nutrition but allows fetuses to continue to term. Fetal bone volume is reduced greater than three-fold and the number of osteoclasts is increased six-fold, resulting in severe osteopenia of perinatal bone. Astrocyte numbers are reduced in the spinal cord and brain stem. Late gestation fetal livers contain relatively high stores of glycogen, indicating a metabolic disorder. Hematologic and primordial germ cell compartments appear normal. Pleiotropic defects in the mutant animals preclude survival beyond the day of birth.
CSF-1 and mouse preimplantation development in vitro
Authors: Bhatnagar Piyush , Papaioannou Virginia E. , Biggers John D. 
Published: April 2021

ABSTRACT
The effects of macrophage colony stimulating factor on the development of the zygote to the blastocyst stage of an outbred strain of mouse have been studied in KSOM, an improved medium that supports a high rate of in vitro development. Macrophage colony stimulating factor accelerates the formation of the blastocyst cavity by day 4 (96 hours post-hCG). It also increases overall embryonic cell number through a differential increase in the number of trophoblast cells, with no significant effect on the number of inner cell mass cells. By day 5 of culture (120 hours posthCG), colony stimulating factor-treated embryos have about 20 more trophoblast cells than control embryos, an increase of about 30 percent of the total number of cells in a control blastocyst. The maximum response of embryos was obtained at a concentration around 540 U ml−1 colony stimulating factor (=918 Stanley units ml−1), and the cytokine can produce the same effects even if it is present in the medium for only part of the culture period. This in vitro stimulation of preimplantation development with macrophage colony stimulating factor is compatible with continued normal fetal development in vivo.
Muscle sensory neurons require neurotrophin-3 from peripheral tissues during the period of normal cell death
Authors: Oakley R. A. , Garner A. S. , Large T. H. , Frank E. 
Published: April 2021

ABSTRACT
To determine if muscle sensory neurons require neurotrophin-3 (NT3) during the period of normal cell death, we used an NT3-specific antiserum to deplete NT3 from peripheral tissues during this period in chick embryos. DiI staining of dorsal roots indicated that limb injections of anti-NT3 reduced the spinal projection of muscle spindle afferents. In contrast, injection of the antiserum into the spinal cord had no demonstrable effect, indicating that the reduced projection following limb injection was due to peripheral blockade of NT3 signaling. Counts of neurons retrogradely labeled from muscle and cutaneous nerves showed that peripheral blockade of NT3 selectively reduced the survival of muscle sensory neurons without affecting the survival of cutaneous sensory neurons or motoneurons. In situ hybridization with trkC probes indicated that, during the period of cell death, most large diameter muscle sensory neurons express trkC transcripts, whereas few cutaneous neurons express this receptor for NT3. We conclude that large diameter muscle afferents, including spindle afferents, require NT3 from peripheral tissues to survive the normal period of sensory neuron death in vivo.
Axonal guidance in the chicken retina
Authors: Stier Heike , Schlosshauer Burkhard 
Published: April 2021

ABSTRACT
During retina development, ganglion cells extend their axons exclusively into the innermost tissue layer, but not into outer retina layers.
In order to elucidate guiding mechanisms for axons, tissue strips of embryonic chicken retinae were explanted onto retinal cryosections (cryoculture). Ganglion cell axons originating from the explant grew preferentially on the innermost retina layer of cryosections, whereas outer tissue layers were avoided, very much as in vivo.
Stereotropism, interaction with laminin of the basal lamina and axonal fasciculation did not significantly affect oriented axonal outgrowth, so that stereotropism as a guidance mechanism could be excluded. Ganglion cell axons were not directed by physical barriers, e.g. microstructured silicon oxide chips. Similarly, UV induced protein inactivation revealed that laminin present in the inner retina did not provide a guidance cue. Even in the absence of ganglion cell axons in retinal cryosections due to prior optic nerve transection in ovo, the growth preference for the innermost retina layer was maintained in cryocultures.
However, oriented elongation of axons along the innermost retina layer was lost when radial glial endfeet were selectively eliminated in retinal cryosections. In addition, glial endfeet provided an excellent growth substratum when pure preparations of endfeet were employed in explant cultures. The preference for glial endfeet positioned at the inner retina surface was accompanied by the avoidance of outer retina layers, most likely because of inhibitory components in this region. This assumption is corroborated by the finding that addition of exogenous growth-promoting laminin to cryosections did not abolish the inhibition. Laminin on glass surfaces provided an excellent substratum. Axonal outgrowth was also seriously hampered on specifically purified cells of the outer retina. Most notable, however, in cryocultures aberrant innervation of outer retina layers could be induced by prior heat or protease treatment of cryosections, which pointed to proteins as potential inhibitory components.
In summary the data substantiate the hypothesis that within the retina, ganglion cell axons are guided by a dual mechanism based on a permissive and an inhibitory zone. Radial glia is likely to be instructive in this process.
Specification of anterior-posterior differences within the AB lineage in the C. elegans embryo: a polarising induction
Authors: Hutter Harald , Schnabel Ralf 
Published: April 2021

ABSTRACT
In a C. elegans embryo the third cleavages of descendants of the anterior blastomere AB of the 2-cell stage create pairs of blastomeres that develop differently. By laser ablation experiments we show that the fates of all the posterior daughters of this division depend on an induction occurring three cleavages before these blastomeres are born. The time of induction precludes a direct effect on cell fate. Alternatively, we suggest that the induction creates a heritable cell polarity which is propagated through several divisions. We suggest a model to demonstrate how a signal could be propagated through several rounds of cell division. An important implication of our observations is that this early induction acts to specify blastomere identity, not tissue type. A detailed lineage analysis revealed that altering the inductive signal alters complex lineage patterns as a whole. The induction described here, together with two inductions described previously can be used to illustrate how the anterior portion of the C. elegans embryo can be successively subdivided into blastomeres with unique developmental potential.
Discrete Polycomb-binding sites in each parasegmental domain of the bithorax complex
Authors: Chiang Anne , O’Connor Michael B. , Paro Renato , Simon Jeff , Bender Welcome 
Published: April 2021

ABSTRACT
The Polycomb protein of Drosophila melanogaster maintains the segmental expression limits of the homeotic genes in the bithorax complex. Polycomb-binding sites within the bithorax complex were mapped by immunostaining of salivary gland polytene chromosomes. Polycomb bound to four DNA fragments, one in each of four successive parasegmental regulatory regions. These fragments correspond exactly to the ones that can maintain segmentally limited expression of a lacZ reporter gene. Thus, Polycomb acts directly on discrete multiple sites in bithorax regulatory DNA. Constructs combining fragments from different regulatory regions demonstrate that Polycomb-dependent maintenance elements can act on multiple pattern initiation elements, and that maintenance elements can work together. The cooperative action of maintenance elements may motivate the linear order of the bithorax complex.
Regulation of HoxA expression in developing and regenerating axolotl limbs
Authors: Gardiner David M. , Blumberg Bruce , Komine Yuriko , Bryant Susan V. 
Published: April 2021

ABSTRACT
Homeobox genes are important in the regulation of outgrowth and pattern formation during limb development. It is likely that homeobox genes play an equally important role during limb regeneration. We have isolated and identified 17 different homeobox-containing genes expressed by cells of regenerating axolotl limbs. Of these, nearly half of the clones represent genes belonging to the HoxA complex, which are thought to be involved in pattern formation along the proximal-distal limb axis. In this paper we report on the expression patterns of two 5′ members of this complex, HoxA13 and HoxA9. These genes are expressed in cells of developing limb buds and regenerating blastemas. The pattern of expression in developing axolotl limb buds is comparable to that in mouse and chick limb buds; the expression domain of HoxA13 is more distally restricted than that of HoxA9. As in developing mouse and chick limbs, HoxA13 likely functions in the specification of distal limb structures, and HoxA9 in the specification of more proximal structures. In contrast, during regeneration, HoxA13 and HoxA9 do not follow the rule of spatial colinearity observed in developing limbs. Instead, both genes are initially expressed in the same population of stump cells, giving them a distal Hox code regardless of the level of amputation. In addition, both are reexpressed within 24 hours after amputation, suggesting that reexpression may be synchronous rather than temporally colinear. Treatment with retinoic acid alters this Hox code to that of a more proximal region by the rapid and differential downregulation of HoxA13, at the same time that expression of HoxA9 is unaffected. HoxA reexpression occurs prior to blastema formation, 24-48 hours after amputation, and is an early molecular marker for dedifferentiation.
Expression of zebrafish nk2.2 is influenced by sonic hedgehog/vertebrate hedgehog-1 and demarcates a zone of neuronal differentiation in the embryonic forebrain
Authors: Barth Katrin Anukampa , Wilson Stephen W. 
Published: April 2021

ABSTRACT
We have isolated zebrafish nk2.2, a member of the Nk-2 family of homeobox genes. nk2.2 is expressed in a continuous narrow band of cells along a boundary zone demarcating the location at which two of the earliest nuclei in the brain differentiate. This band of cells is located within a few cell diameters of cells expressing the signalling molecule sonic hedgehog/vertebrate hedgehog-1 (shh/vhh-1). Injection of shh/vhh-1 RNA results in ectopic expression of nk2.2 and concomitant abnormalities in the forebrain and eyes. Moreover, cyclops mutant embryos, which initially lack neurectodermal expression of shh/vhh-1, show a concomitant lack of nk2.2 expression. Together, these results suggest a requirement of shh/vhh-1 protein for the spatial regulation of nk2.2 expression.
Temporal regulation of the Xenopus FGF receptor in development: a translation inhibitory element in the 3′ untranslated region
Authors: Robbie Edward P. , Peterson Michael , Amaya Enrique , Musci Thomas J. 
Published: April 2021

ABSTRACT
Early frog embryogenesis depends on a maternal pool of mRNA to execute critical intercellular signalling events. FGF receptor-1, which is required for normal development, is stored as a stable, untranslated maternal mRNA transcript in the fully grown immature oocyte, but is translationally activated at meiotic maturation. We have identified a short cis-acting element in the FGF receptor 3′ untranslated region that inhibits translation of synthetic mRNA. This inhibitory element is sufficient to inhibit translation of heterologous reporter mRNA in the immature oocyte without changing RNA stability. Deletion of the poly(A) tract or polyadenylation signal sequences does not affect translational inhibition by this element. At meiotic maturation, we observe the reversal of translational repression mediated by the inhibitory element, mimicking that seen with endogenous maternal FGF receptor mRNA at meiosis. In addition, the activation of synthetic transcripts at maturation does not appear to require poly(A) lengthening. We also show that an oocyte cytoplasmic protein specifically binds the 3′ inhibitory element, suggesting that translational repression of Xenopus FGF receptor-1 maternal mRNA in the oocyte is mediated by RNA-protein interactions. These data describe a mechanism of translational control that appears to be independent of poly(A) changes.
nanos is an evolutionarily conserved organizer of anterior-posterior polarity
Authors: Curtis, Daniel , Apfeld Javier , Lehmann Ruth 
Published: April 2021

ABSTRACT
In Drosophila melanogaster, nanos functions as a localized determinant of posterior pattern. Nanos RNA is localized to the posterior pole of the maturing egg cell and encodes a protein that emanates from this localized source. Nanos acts as a translational repressor and thereby establishes a gradient of the morphogen Hunchback. Here we show that the mechanism by which nanos acts in Drosophila is a common developmental strategy in Dipteran insects. We used cytoplasmic transplantation assays to demonstrate that nanos activity is found in posterior poleplasm of five diverse Dipteran species. Genes homologous to nanos were identified from Drosophila virilis, the housefly Musca domestica, and the midge Chironomus samoensis. These genes encode RNAs that are each localized, like nanos, to the embryonic posterior pole. Most importantly, we demonstrate that these homologues can functionally substitute for nanos in D. melanogaster. These results suggest that nanos acts in a similar pathway for axis determination in other insects. Comparison of the Nanos sequences reveals only 19% overall protein sequence similarity; high conservation of a novel zinc finger near the carboxy terminus of the protein defines a region critical for nanos gene function.
Intracellular acidification of gastrula ectoderm is important for posterior axial development in Xenopus
Authors: Gutknecht D. R. , Koster C. H. , Tertoolen L. G. J. , Laat S. W. de , Durston A. J. 
Published: April 2021

ABSTRACT
There is evidence suggesting that pHi elevation can induce differentiation to cement gland, an extremely anterior structure, during the early development of Xenopus laevis (Picard, J. J. (1975) J. Embryol. exp. Morphol. 33, 957-967; Sive, H. L., Hattori, K. and Weintraub, H. (1989) Cell 58, 171-180). We wanted to investigate whether axial development or neural induction are mediated in Xenopus via regulation of pHi. Our interest was stimulated further because certain signal transduction pathways, which are thought to mediate anterior neural induction (Otte, A. P., Van Run, P., Heideveld, M., Van Driel, R. and Durston, A. J. (1989) Cell 58, 641-648; Durston and Otte (1991), Cell-Cell Interactions in Early Development, pp. 109-127), are also known to modify the activity of proton extruders (Mitsuka and Berk (1991)Am. J. Physiol. 260, C562-C569; Wakabayashi, S., Sardet, C., Fafournoux, P., Counillon, L., Meloche, S., Pages, G. and Pouysségur, J. (1993) Rev. Physiol. Biochem. Pharmacol. Vol. 119, pp. 157-186). We therefore measured pHi in explants of gastrula ectoderm and neurectoderm and identified ion exchangers that regulate pHi in these tissues. The measurements showed that pHi decreases in explants of both neurectoderm and uninduced ectoderm during the time course of gastrulation, this pHi decrease thus fails to correlate with neural induction. One important regulator of this cytoplasmic acidification is the Na+/H+ exchanger. The pHi set point, at which the acid extrusion activity of this alkalizing exchanger is shut off, shifts to more acidic values during the time course of gastrulation, thus permitting cytoplasmic acidification. We found also that preventing cytoplasmic acidification and thereby elevating pHi in late gastrula cells led to the specific suppression of posterior development. Neural induction and anterior development were unaffected by treatments leading either to an elevation of or a decrease in pHi. These findings indicate that the cellular processes mediating anterior development and neural induction are pHi tolerant, while the signals mediating posterior development require a sustained pHi decrease for their action, suggesting that downregulation of pHi is nescessary for posterior axial development.
Cis-regulatory control of the SM50 gene, an early marker of skeletogenic lineage specification in the sea urchin embryo
Authors: Makabe Kazuhiro W. , Kirchhamer Carmen V. , Britten Roy J. , Davidson Eric H. 
Published: April 2021

ABSTRACT
The SM50 gene encodes a minor matrix protein of the sea urchin embryo spicule. We carried out a detailed functional analysis of a cis-regulatory region of this gene, extending 440 bp upstream and 120 bp downstream of the transcription start site, that had been shown earlier to confer accurate skeletogenic expression of an injected expression vector. The distal portion of this fragment contains elements controlling amplitude of expression, while the region from −200 to +105 contains spatial control elements that position expression accurately in the skeletogenic lineages of the embryo. A systematic mutagenesis analysis of this region revealed four adjacent regulatory elements, viz two copies of a positively acting sequence (element D) that are positioned just upstream of the transcription start site; an indispensable spatial control element (element C) that is positioned downstream of the start site; and further downstream, a second positively acting sequence (element A). We then constructed a series of synthetic expression constructs. These contained oligonucleotides representing normal and mutated versions of elements D, C, and A, in various combinations. We also changed the promoter of the SM50 gene from a TATA-less to a canonical TATA box form, without any effect on function. Perfect spatial regulation was also produced by a final series of constructs that consisted entirely of heterologous enhancers from the CyIIIa gene, the SV40 early promoter, and synthetic D, C, and A elements. We demonstrate that element C exercises the primary spatial control function of the region we analyzed. We term this a ‘locator’ element. This differs from conventional ‘tissue-specific enhancers’ in that while it is essential for expression, it has no transcriptional activity on its own, and it requires other, separable, positive regulatory elements for activity. In the normal configuration these ancillary positive functions are mediated by elements A and D. Only positively acting control elements were observed in the SM50 regulatory domain throughout this analysis.
Identification of a neurogenic sublineage required for CNS segmentation in an Annelid
Authors: Ramírez Felipe-Andrés , Wedeen Cathy J. , Stuart Duncan K. , Lans Deborah , Weisblat David A. 
Published: April 2021

ABSTRACT
In embryos of leeches (phylum Annelida), metameric structures arise sequentially from a germinal plate comprising the descendants of five pairs of embryonic stem cells called teloblasts. It has been shown that transverse stripes of cells expressing ht-en (a homolog of engrailed, a Drosophila segment polarity gene), arise in the germinal plate prior to the appearance of segmental ganglia and that, in the main neurogenic lineage (derived from the N teloblasts), the stripe of cells expressing ht-en demarcates the boundary between prospective segmental ganglia. Previous lineagetracing experiments had suggested that the clones of nf and ns primary blast cells in the N lineage are confined to within segmental borders. This conclusion was called into question by the observation that the cells expressing ht-en do not appear to be at the very posterior edge of the nf clone, from which they arise. To resolve this issue, we have injected individual primary blast cells with fluorescent lineage tracers; we find that cells in the nf clone actually straddle two adjacent ganglia. Moreover, using photoablation techniques, we find that the nf clone is required for proper morphogenesis of the segmentally iterated central nervous system (CNS).
phantastica: a gene required for dorsoventrality of leaves in Antirrhinum majus
Authors: Waites Richard , Hudson Andrew 
Published: April 2021

ABSTRACT
To understand better the mechanisms that lead to dorsoventrality in the lateral organs of plants, mutants at the phantastica (phan) locus of Antirrhinum majus have been identified and characterised. The leaves, bracts and petal lobes of phan mutants show varying degrees of reduction in dorsal tissues, indicating that phan is required for establishing dorsal cell identity. Each phan mutant produces a variety of different leaf morphologies, but has a characteristic and relatively constant floral phenotype. In several different forms of phan mutant leaves and petal lobes, novel boundaries between dorsal and ventral cell types form ectopic axes of growth, suggesting that phan-dependent dorsal cell identity is required for lateral growth of the wild-type leaf and petal lobe. Comparisons between the development of wild-type and mutant petals or leaves reveal that phan acts early in development of these lateral organs. The possible role of the phan gene in evolution of different leaf forms is discussed.