bluuebunny/crossref_metadata_2025_split huggingface dataset:
Apoptosis is a generator of Wnt-dependent regeneration and homeostatic cell renewal in the ascidian Ciona
Authors: Jeffery William R. , Gorički Špela 
Published: April 2021

ABSTRACT
In the ascidian Ciona intestinalis, basal body parts regenerate distal structures but distal body parts do not replace basal structures. Regeneration involves the activity of adult stem cells in the branchial sac, which proliferate and produce migratory progenitor cells for tissue and organ replacement. Branchial sac-derived stem cells also replenish recycling cells lining the pharyngeal fissures during homeostatic growth. Apoptosis at injury sites occurs early during regeneration and continuously in the pharyngeal fissures during homeostatic growth. Caspase 1 inhibitor, caspase 3 inhibitor, or pan-caspase inhibitor Z-VAD-FMK treatment blocked apoptosis, prevented regeneration, and suppressed branchial sac growth and function. A pharmacological screen and siRNA-mediated gene knockdown indicated that regeneration requires canonical Wnt signaling. Wnt3a protein rescued both caspase-blocked regeneration and branchial sac growth. Inhibition of apoptosis did not affect branchial sac stem cell proliferation but prevented the survival of progenitor cells. After bisection across the mid-body, apoptosis occurred only in the regenerating basal fragments, although both fragments contained a part of the branchial sac, suggesting that apoptosis is unilateral at the wound site and the presence of branchial sac stem cells is insufficient for regeneration. The results suggest that apoptosis-dependent Wnt signaling mediates regeneration and homeostatic growth in Ciona.
The induction of anterior and posterior neural genes in Xenopus laevis
Authors: Sharpe C. R. , Gurdon J. B. 
Published: April 2021

Abstract
We have investigated the interactions between mesoderm and ectoderm that result in the formation of a regionally differentiated nervous system in Xenopus embryos. We have used genes expressed at different positions along the neural tube as regional markers of neural induction in both whole, and in experimentally manipulated embryos. By comparing transcription from the anterior marker, XIF3, with that from the posterior marker, XIHbox6, and the general neural marker XIF6, we have shown that the normal induction process requires interactions between ectoderm and mesoderm that persist through gastrulation into the late neurula stages.
We have found that competence of the ectoderm to respond to induction is lost at the same early neurula stage for all three marker genes. Using rhodamine dextran-labelled mesoderm, we have established that the duration of contact between ectoderm and mesoderm required for gene activation in conjugates is the same for each of the markers. We have, however, identified regions of the mesoderm that can induce different combinations of neural marker gene expression. The anterior mesoderm induces expression of the anterior marker, XIF3, and the later migrating posterior mesoderm induces the ectoderm overlying it to express the posterior marker XIHbox6.
It has been proposed that neural inducing signals reach the ectoderm by two different routes: from mesoderm lying directly beneath the ectoderm or along the plane of the ectoderm. We have assessed the contribution of each route in respect of our three neural markers and find that a signal passing directly from mesoderm to ectoderm fully accounts for neural gene expression. We were unable to detect an inducing signal that passes along the plane of the ectoderm.
Single cell transplantation reveals interspecific cell communication in Drosophila chimeras
Authors: Becker Thomas , Technau Gerhard M. 
Published: April 2021

Abstract
Cell –cell communication is not only a common strategy for cell fate specification in vertebrates, but plays important roles in invertebrate development as well. We report here on experiments testing the compatibility of mechanisms specifying cell fate among six different Drosophila species. Following interspecific transplantation, the development of single ectodermal cells was traced in order to test their abilities to proliferate and differentiate in a heterologous environment. Despite considerable differences in cell size and length of cell cycle among some of the species, the transplants gave rise to fully differentiated clones that were integrated into the host tissue. Clones comprised cells of epidermal and/or neural histotypes, indicating that mechanisms mediating the epidermal/neural dichotomy in the ectoderm are conserved between the species. Cells of the neural lineages differentiated into neurones, glia, or both. Moreover, heterologous neurones sent out axons that followed major pathways along nerves and within the neuropile, demonstrating their ability to recognize positional cues in the heterologous CNS of the host.
Expression of the tyrosine kinase receptor gene trkB is confined to the murine embryonic and adult nervous system
Authors: Klein Rüdiger , Martin-Zanca Dionisio , Acid Mariano Barb , Parada Luis F. 
Published: April 2021

Abstract
We have examined the expression of the trkB gene, which encodes a member of the family of protein tyrosine kinase (TK) transmembrane receptors, during mouse embryogenesis using in situ hybridization and Northern analysis. Transcripts were first detected in the neuroepithelium and in the neural crest of 9.5 day embryos with regions of high expression in the neural folds and at the lateral neuroepithelium. However, during the process of cephalization and development of the peripheral nervous system, transcripts were detected in most neural tissues, including the brain, spinal cord, cranial and spinal ganglia, and along the pathways of axonal tracts extending peripherally. In the adult brain, expression continues in a complex pattern that is confined to specific regions or neuron types. The expression of trkB, a TK receptor, in early embryogenesis, and specifically in neural tissues, is consistent with the notion that this gene plays a role in the events that regulate the development of the nervous system.
Expression of the neuronal surface glycoprotein Thy-1 is under post-transcriptional control, and is spatially regulated, in the developing olfactory system
Authors: Xue G. P. , Calvert R. A. , Morris R. J. 
Published: April 2021

Abstract
Expression of the neuronal cell surface glycoprotein Thy-1 has been studied during the development of the olfactory bulb in mice and rats, using in situ hybridisation and immunohistochemistry to follow the appearance of Thy-1 mRNA and protein, respectively. The mRNA was first detected 4 days before birth on all mitral cells, the main projection neuron of the bulb, as they formed a distinct layer and grew dendrites. At no stage was any spatial gradient of expression of Thy-1 mRNA evident around the mitral cell layer. Thy-1 protein, on the other hand, was first detectable 2 days later on a group of mitral cells immediately adjacent the point of entry of the olfactory nerve. The numbers of immunoreactive cells spread, over the next 7 days, to include all mitral cells, those located rostrally and laterally in the bulb being slowest to express Thy-1 protein. Thus there was a spatiotemporal gradient of expression of Thy-1 protein, which was not apparent in the earlier general expression of its mRNA, suggesting that some further inductive signal was required after transcription in order to get effective production of protein. Analysis of the growth of the mitral cell axons in the lateral olfactory tract suggested this signal was related to the cessation of axonogenesis, as Thy-1 immunoreactivity became detectable on these axons only when their expression of the transient epitope detected by the GIO antibody, present on microtubule-associated protein (MAP)lx only during axonal growth, declined.
For the first week after Thy-1 protein appeared on mitral cells, it was not distributed uniformally on their surface. Immunoreaction was relatively weak on the somatic surface, and the molecule appeared to be entirely excluded from the distal regions of its main dendrite, above the outer plexiform layer. Here the dendrite reaches up to the synaptic glomeruli formed with the incoming olfactory nerve axons. These distal regions of the dendritic shaft became immunoreactive only after the periglomerular cells had first begun to express Thy-1 protein in the glomeruli. Immunolabelling of the somatic membrane then increased, to give the adult pattern of uniform Thy-1 labelling of the neuronal membrane by the end of the second postnatal week. It is suggested that some of the molecular features of Thy-1, and anatomical features of the main bulb, could interact to produce this initial restriction of Thy-1 to particular parts of the mitral cell suface.
Despite the mitral cells of the accessory olfactory bulb developing earlier than those of the main bulb, both Thy-1 mRNA and protein appeared 5 –7 days later on the cells of the accessory bulb. This may be related to the guidance role that the accessory axons are thought to play in respect of the later developing fibres of the main bulb.
Localization of the DER/flb protein in embryos: implications on the faint little ball lethal phenotype
Authors: Zak Naomi B. , Wides Ronald J. , Schejter Eyal D. , Raz Erez , Shilo Ben-Zion 
Published: April 2021

Abstract
Antibodies were raised against the Drosophila EGF receptor homolog (DER) and used for immunohistochemical analyses of Drosophila embryos. We found that DER is localized in a wide array of embryonic tissues, displaying a dynamic pattern of expression. DER appears to be expressed in all cells at the cellular blastoderm and gastrula stages. In extended-germ-band embryos, it is found predominantly in the mesoderm and the head. Finally, in retracted-germ-band embryos, DER immunoreactivity is most pronounced at sites of somatic muscle attachments and along the ventral midline of the CNS. We have thus observed that DER is expressed in the diverse tissues which are affected in the DER faint little ball (flb) embryonic lethal phenotype. The different pattern and extent of expression in each tissue suggests that the disparate aspects of the flb phenotype may result from different mechanisms of DER function. To understand the basis for the CNS phenotype of DER/flb mutants, we have closely followed the collapse of the CNS in mutant embryos. Our observations on the evolution of the final CNS phenotype, in combination with the temporo-spatial pattern of appearance of DER in the ventral neuroepithelium, suggest that this receptor participates in the second phase of neuron– glia interactions, namely in stabilization of the ladder-like CNS scaffolding formed by outgrowth of pioneer axonal processes along the glial pre-pattern.
The Notch locus of Drosophila is required in epidermal cells for epidermal development
Authors: Hoppe Pamela E. , Greenspan Ralph J. 
Published: April 2021

Abstract
The Notch locus of Drosophila plays an important role in cell fate decisions within the neurogenic ectoderm, a role thought to involve interactions at the cell surface. We have assayed the requirement for Notch gene expression in epidermal cells by two kinds of genetic mosaics. First, with gynandromorphs, we removed the wild-type gene long before the critical developmental events to produce large mutant clones. The genotype of cells in large clones was scored by means of an antibody to the Notch protein. Second, using mitotic recombination, we removed the gene at successively later times after completion of the mitotically active early cleavage stages, to produce small clones. These clones were detected by means of a linked mutation of cuticle pattern, armadillo. The results of both experiments demonstrate a requirement for Notch expression by epidermal cells, and thus argue against the model that the Notch product acts as a signal required only in the neuroblast to influence neighboring epidermal cells. The mitotic recombination experiment revealed that Notch product is required by epidermal cells subsequent to neuroblast delamination. This result implies that the Notch gene functions to maintain the determined state of epidermal cells, possibly by mediating cell surface interactions within the epidermis.
Tentacle morphogenesis in hydra: I. The role of head activator
Authors: Hobmayer Engelbert , Holstein Thomas W. , David Charles N. 
Published: April 2021

Abstract
Stimulation of tentacle-specific cell differentiation by the neuropeptide head activator was investigated in Hydra magnipapillata. Tentacle-specific sensory nerve cells were identified by a monoclonal antibody, NV1. Treatment of hydra with 1 pM head activator for 18 h stimulated differentiation of NV1+ nerve cells and tentacle epithelial cells in tissue from the distal gastric region. Head tissue and tissue from the proxmial gastric region did not respond to head activator treatment with increased NV1+ differentiation. Hence the distal gastric region appears to be the site of tentacle formation in hydra. Tentacle precursors in head tissue seem to be committed since they fail to respond to head activator or to changes in tissue size with altered amounts of tentacle formation. We suggest that NV1 precursors form a complex with tentacle epithelial cell precursors, which then moves distally through the head region into the tentacles. The signal for NV1+ differentiation appears to be formation of this complex.
Interaction between satellite cells and skeletal muscle fibers
Authors: Bischoff Richard 
Published: April 2021

Abstract
Single myofibers with attached satellite cells isolated from adult rats were used to study the influence of the mature myofiber on the proliferation of satellite cells. The satellite cells remain quiescent when cultured in serum containing medium but proliferate when exposed to mitogen from an extract of crushed adult muscle. The response of satellite cells to mitogen was measured under three situations with respect to cell contact: (1) in contact with a viable myofiber and its basal lamina, (2) detached from the myofiber by centrifugal force and deposited on the substratum and (3) beneath the basal lamina of a Marcaine killed myofiber. The results show that satellite cells in contact with the plasmalemma of a viable myofiber have reduced mitogenic response. Since inhibiting growth may induce differentiation, I tested whether satellite cells proliferating on the surface of a myofiber would fuse. Although the satellite cell progeny were fusion competent, they did not fuse with the myofiber. To determine whether fusion competence of the myofiber changes with time in culture, embryonic myoblasts were challenged to fuse with myofibers that had been stripped of satellite cells and cultured for several days. The myoblasts fused with pseudopodia! sprouts growing from the ends of the myofiber, but did not fuse with the original myofiber surface. These results indicate that contact with the surface of a mature myofiber suppresses proliferation of myogenic cells but the cells do not fuse with the myofiber.
Double anterior chick limb buds and models for cartilage rudiment specification
Authors: Wolpert Lewis , Hornbruch Amata 
Published: April 2021

AbstractMost models for the specification of the skeletal elements in the developing limb bud are based on a chemical specification well before overt cartilage differentiation. By contrast, a physico-mechanical model proposes that the process of condensation – an early feature of cartilage differentiation – is itself the basis for patterning the elements. The models thus make quite different predictions as to when the rudiments are specified. Double anterior limb buds have been constructed at stages earlier than condensation, with the expectation that, if specification of the humerus occurs before cartilage condensation, then limbs containing two humeri should develop, since the presumptive humerus lies largely in the anterior region. The development of anterior and posterior parts, on their own, was in general, consistent with the fate map; both developed a humerus that was thinner than normal. Double anterior limbs developed two humeri in 28 % of cases and a much thicker humerus in 39 %. These results strongly support models based on an early specification of limb rudiments and cannot be accounted for by the physical model. Double anterior limbs in which the two parts were from different stages, developed such that a digit 3 could lie adjacent to the radius, giving further striking evidence for early specification and local autonomy of development.
Identification in Xenopus of a structural homologue of the Drosophila gene Snail
Authors: Sargent Michael G. , Bennett Michael F. 
Published: April 2021

Abstract
We have cloned a Xenopus cDNA that is related to snail, a gene that is required for mesoderm formation in Drosophila. The cDNA encodes a protein that contains five zine-fingers that closely resemble those of snail. In the non-canonical parts of the DNA-binding loop, there is almost 90 % homology between snail and xsna. The corresponding mRNA (xsna) is expressed strongly at the start of zygotic transcription simultaneously with the transcription factor EFla. In early gastrulae, xsna is equally distributed between the dorsal and ventral halves of the equatorial zone. The possibility that the capacity to synthesise xsna is more localised before the start of zygotic transcription has been investigated by culturing fragments of stage 8 embryos until xsna is synthesised. The capacity to synthesise xsna at stage 8 is located principally in the dorsal half of the equatorial zone. A small amount of maternal xsna is localised in the vegetal hemisphere before zygotic transcription starts. xsna is not present in isolated animal caps but can be induced by the mesoderm-inducing factors XTC-MIF and bFGF. Synthesis of xsna does not occur autonomously in dispersed cells but is restored when cells reaggregate in the presence of calcium and magnesium.
pax2.1is required for the development of thyroid follicles in zebrafish
Authors: Wendl Thomas , Lun Klaus , Mione Marina , Favor Jack , Brand Michael , Wilson Stephen W. , Rohr Klaus B. 
Published: April 2021

The thyroid gland is an organ primarily composed of endoderm-derived follicular cells. Although disturbed embryonic development of the thyroid gland leads to congenital hypothyroidism in humans and mammals, the underlying principles of thyroid organogenesis are largely unknown. In this study, we introduce zebrafish as a model to investigate the molecular and genetic mechanisms that control thyroid development. Marker gene expression suggests that the molecular pathways of early thyroid development are essentially conserved between fish and mammals. However during larval stages, we find both conserved and divergent features of development compared with mammals. A major difference is that in fish, we find evidence for hormone production not only in thyroid follicular cells, but also in an anterior non-follicular group of cells.We show that pax2.1 and pax8, members of the zebrafish pax2/5/8 paralogue group, are expressed in the thyroid primordium. Whereas in mice, only Pax8 has a function during thyroid development, analysis of the zebrafish pax2.1 mutant no isthmus (noi–/–) demonstrates that pax2.1 has a role comparable with mouse Pax8 in differentiation of the thyroid follicular cells. Early steps of thyroid development are normal in noi–/–, but later expression of molecular markers is lost and the formation of follicles fails. Interestingly, the anterior non-follicular site of thyroid hormone production is not affected in noi–/–. Thus, in zebrafish, some remaining thyroid hormone synthesis takes place independent of the pathway leading to thyroid follicle formation. We suggest that the noi–/– mutant serves as a new zebrafish model for hypothyroidism.
Mathematical modeling of the interaction between yolk utilization and fish growth in zebrafish,Danio rerio
Authors: Schwartz Ashley V. , Sant Karilyn E. , Navarrete Julian , George Uduak Z. 
Published: April 2021

ABSTRACTOptimal embryonic development plays a major role in the health of an individual beyond the developmental stage. Nutritional perturbation during development is associated with cardiovascular and metabolic disease later in life. With both nutritional uptake and overall growth being risk factors for eventual health, it is necessary to understand not only the behavior of the processes during development but also their interactions. In this study, we used differential equations, image analyses, curve fittings, parameter estimation and laboratory experiments to quantify the rate of yolk absorption and its effect on early development of a vertebrate model (Danio rerio). Findings from this study establish a nonlinear functional relationship between nutrient absorption and early fish growth. We found that the rate of change in fish length and yolk utilization is logistic, that is the yolk decays rapidly for a period of time before leveling out. An interesting finding from this study is that yolk utilization reaches its maximum at 84 h post-fertilization. We validated our mathematical models against experimental observations, making them powerful tools for replication and future simulations.
Cis-regulatory dissection of cone development reveals a broad role for Otx2 and Oc transcription factors
Authors: Lonfat Nicolas , Wang Su , Lee ChangHee , Garcia Mauricio , Choi Jiho , Park Peter J. , Cepko Connie 
Published: April 2021

ABSTRACT
The vertebrate retina is generated by retinal progenitor cells (RPCs), which produce &gt;100 cell types. Although some RPCs produce many cell types, other RPCs produce restricted types of daughter cells, such as a cone photoreceptor and a horizontal cell (HC). We used genome-wide assays of chromatin structure to compare the profiles of a restricted cone/HC RPC and those of other RPCs in chicks. These data nominated regions of regulatory activity, which were tested in tissue, leading to the identification of many cis-regulatory modules (CRMs) active in cone/HC RPCs and developing cones. Two transcription factors, Otx2 and Oc1, were found to bind to many of these CRMs, including those near genes important for cone development and function, and their binding sites were required for activity. We also found that Otx2 has a predicted autoregulatory CRM. These results suggest that Otx2, Oc1 and possibly other Onecut proteins have a broad role in coordinating cone development and function. The many newly discovered CRMs for cones are potentially useful reagents for gene therapy of cone diseases.
A multi-gene knockdown approach reveals a new role for Pax6 in controlling organ number in Drosophila
Authors: Ordway Alison J. , Teeters Gary M. , Weasner Bonnie M. , Weasner Brandon P. , Policastro Robert , Kumar Justin P. 
Published: April 2021

ABSTRACT
Genetic screens are designed to target individual genes for the practical reason of establishing a clear association between a mutant phenotype and a single genetic locus. This allows for a developmental or physiological role to be assigned to the wild-type gene. We previously observed that the concurrent loss of Pax6 and Polycomb epigenetic repressors in Drosophila leads the eye to transform into a wing. This fate change is not seen when either factor is disrupted separately. An implication of this finding is that standard screens may miss the roles that combinations of genes play in development. Here, we show that this phenomenon is not limited to Pax6 and Polycomb but rather applies more generally. We demonstrate that in the Drosophila eye-antennal disc, the simultaneous downregulation of Pax6 with either the NURF nucleosome remodeling complex or the Pointed transcription factor transforms the head epidermis into an antenna. This is a previously unidentified fate change that is also not observed with the loss of individual genes. We propose that the use of multi-gene knockdowns is an essential tool for unraveling the complexity of development.