bluuebunny/crossref_metadata_2025_split huggingface dataset:
A novel WD40 protein, CHE-2, acts cell-autonomously in the formation of C. elegans sensory cilia
Authors: Fujiwara Manabi , Ishihara Takeshi , Katsura Isao 
Published: April 2021

Abstract
To elucidate the mechanism of sensory cilium formation, we analyzed mutants in the Caenorhabditis elegans che-2 gene. These mutants have extremely short cilia with an abnormal posterior projection, and show defects in behaviors that are mediated by ciliated sensory neurons. The che-2 gene encodes a new member of the WD40 protein family, suggesting that it acts in protein-protein interaction. Analysis of mutation sites showed that both the amino-terminal WD40 repeats and the carboxyl-terminal non-WD40 domain are necessary for the CHE-2 function. CHE-2-tagged green fluorescent protein is localized at the cilia of almost all the ciliated sensory neurons. Expression of che-2 in a subset of sensory neurons of a che-2 mutant by using a heterologous promoter resulted in restoration of the functions and cilium morphology of only the che-2-expressing neurons. Thus, che-2 acts cell-autonomously. This technique can be used in the future for determining the function of each type of che-2-expressing sensory neuron. Using green fluorescent protein, we found that the extension of cilia in wild-type animals took place at the late embryonic stage, whereas the cilia of che-2 mutant animals remained always short during development. Hence, the abnormal posterior projection is due to the inability of cilia to extend, rather than degeneration of cilia once correctly formed. Expression of che-2 in a che-2 mutant under a heat shock promoter showed that the extension of cilia, surprisingly, can occur even at the adult stage, and that such cilia can function apparently normally in behavior.
SF/HGF is a mediator between limb patterning and muscle development
Authors: Scaal Martin , Bonafede Alexander , Dathe Verena , Sachs Martin , Cann Gordon , Christ Bodo , Brand-Saberi Beate 
Published: April 2021

Abstract
Scatter factor/hepatocyte growth factor (SF/HGF) is known to be involved in the detachment of myogenic precursor cells from the lateral dermomyotomes and their subsequent migration into the newly formed limb buds. As yet, however, nothing has been known about the role of the persistent expression of SF/HGF in the limb bud mesenchyme during later stages of limb bud development. To test for a potential role of SF/HGF in early limb muscle patterning, we examined the regulation of SF/HGF expression in the limb bud as well as the influence of SF/HGF on direction control of myogenic precursor cells in limb bud mesenchyme. We demonstrate that SF/HGF expression is controlled by signals involved in limb bud patterning. In the absence of an apical ectodermal ridge (AER), no expression of SF/HGF in the limb bud is observed. However, FGF-2 application can rescue SF/HGF expression. Excision of the zone of polarizing activity (ZPA) results in ectopic and enhanced SF/HGF expression in the posterior limb bud mesenchyme. We could identify BMP-2 as a potential inhibitor of SF/HGF expression in the posterior limb bud mesenchyme. We further demonstrate that ZPA excision results in a shift of Pax-3-positive cells towards the posterior limb bud mesenchyme, indicating a role of the ZPA in positioning of the premuscle masses. Moreover, we present evidence that, in the limb bud mesenchyme, SF/HGF increases the motility of myogenic precursor cells and has a role in maintaining their undifferentiated state during migration. We present a model for a crucial role of SF/HGF during migration and early patterning of muscle precursor cells in the vertebrate limb.
fatvg encodes a new localized RNA that uses a 25-nucleotide element (FVLE1) to localize to the vegetal cortex of Xenopus oocytes
Authors: Chan Agnes P. , Kloc Malgorzata , Etkin Laurence D. 
Published: April 2021

Abstract
Vegetally localized transcripts have been implicated in a number of important biological functions, including cell fate determination and embryonic patterning. We have isolated a cDNA, fatvg, which encodes a localized maternal transcript that exhibits a localization pattern reminiscent of Vg1 mRNA. fatvg is the homologue of a mammalian gene expressed in adipose tissues. The fatvg transcript, unlike Vg1 which localizes strictly through the Late pathway, also associates with the mitochondrial cloud that is characteristic of the METRO or Early pathway. This suggests that fatvg mRNA may utilize both the METRO and Late pathways to localize to the vegetal cortex during oogenesis. We have dissected the cis-acting localization elements of fatvg mRNA and compared these elements with Vg1 mRNA. Our results indicate that, like most localized RNAs, in a variety of systems, transcripts of fatvg contain localization elements in the 3′UTR. The 3′UTR of fatvg mRNA contains multiple elements that are able to function independently; however, it functions most efficiently when all of the elements are present. We have defined a short 25-nucleotide element that can direct vegetal localization as a single copy. This element differs in sequence from previously described Vg1 localization elements, suggesting that different localization elements are involved in the localization of RNAs through the Late pathway.
Development of the cardiac conduction system involves recruitment within a multipotent cardiomyogenic lineage
Authors: Cheng Gang , Litchenberg Wanda H. , Cole Gregory J. , Mikawa Takashi , Thompson Robert P. , Gourdie Robert G. 
Published: April 2021

Abstract
The cardiac pacemaking and conduction system sets and maintains the rhythmic pumping action of the heart. Previously, we have shown that peripheral cells of the conduction network in chick (periarterial Purkinje fibers) are selected within a cardiomyogenic lineage and that this recruitment occurs as a result of paracrine cues from coronary arteries. At present, the cellular derivation of other elements of this specialized system (e.g. the nodes and bundles of the central conduction system) are controversial, with some proposing that the evidence supports a neurogenic and others a myogenic origin for these tissues. While such ontological questions remain, it is unlikely that progress can be made on the molecular mechanisms governing patterning and induction of the central conduction system. Here, we have undertaken lineage-tracing strategies based on the distinct properties of replication-incompetent adenoviral and retroviral lacZ-expressing constructs. Using these complementary approaches, it is shown that cells constituting both peripheral and central conduction tissues originate from cardiomyogenic progenitors present in the looped, tubular heart with no detectable contribution by migratory neuroectoderm-derived populations. Moreover, clonal analyses of retrovirally infected cells incorporated within any part of the conduction system suggest that such cells share closer lineage relationships with nearby contractive myocytes than with other, more distal elements of the conduction system. Differentiation birthdating by label dilution using [3H]thymidine also demonstrates the occurrence of ongoing myocyte conscription to conductive specialization and provides a time course for this active and localized selection process in different parts of the system. Together, these data suggest that the cardiac conduction system does not develop by outgrowth from a prespecified pool of ‘primary’ myogenic progenitors. Rather, its assembly and elaboration occur via processes that include progressive and localized recruitment of multipotent cardiomyogenic cells to the developing network of specialized cardiac tissues.
Migration of the Drosophila primordial midgut cells requires coordination of diverse PS integrin functions
Authors: Martin-Bermudo Maria D. , Alvarez-Garcia Ines , Brown Nicholas H. 
Published: April 2021

Abstract
Cell migration during embryogenesis involves two populations of cells: the migrating cells and the underlying cells that provide the substratum for migration. The formation of the Drosophila larval midgut involves the migration of the primordial midgut cells along a visceral mesoderm substratum. We show that integrin adhesion receptors are required in both populations of cells for normal rates of migration. In the absence of the PS integrins, the visceral mesoderm is disorganised, the primordial midgut cells do not display their normal motile appearance and their migration is delayed by 2 hours. Removing PS integrin function from the visceral mesoderm alone results in visceral mesoderm disorganization, but only causes a modest delay in migration and does not affect the appearance of the migrating cells. Removing PS integrin function from the migrating cells causes as severe a delay in migration as the complete loss of PS integrin function. The functions of PS1 and PS2 are specific in the two tissues, endoderm and mesoderm, since they cannot substitute for each other. In addition there is a partial redundancy in the function of the two PS integrins expressed in the endoderm, PS1 (αPS1βPS) and PS3 (αPS3βPS), since loss of just one α subunit in the midgut results in either a modest delay (αPS1) or no effect (αPS3). We have also examined the roles of small GTPases in promoting migration of the primordial midgut cells. We find that dominant negative (N17) versions of Rac and Cdc42 cause a very similar defect in migration as loss of integrins, while those of Rho and Ras have no effect. Thus integrins are involved in mediating migration by creating an optimal substratum for adhesion, adhering to that substratum and possibly by activating Rac and Cdc42.
Polarity of the mouse embryo is anticipated before implantation
Authors: Weber R. J. , Pedersen R. A. , Wianny F. , Evans M. J. , Zernicka-Goetz M. 
Published: April 2021

Abstract
In most species, the polarity of an embryo underlies the future body plan and is determined from that of the zygote. However, mammals are thought to be an exception to this; in the mouse, polarity is generally thought to develop significantly later, only after implantation. It has not been possible, however, to relate the polarity of the preimplantation mouse embryo to that of the later conceptus due to the lack of markers that endure long enough to follow lineages through implantation. To test whether early developmental events could provide cues that predict the axes of the postimplantation embryo, we have used the strategy of injecting mRNA encoding an enduring marker to trace the progeny of inner cell mass cells into the postimplantation visceral endoderm. This tissue, although it has an extraembryonic fate, plays a role in axis determination in adjacent embryonic tissue. We found that visceral endoderm cells that originated near the polar body (a marker of the blastocyst axis of symmetry) generally became distal as the egg cylinder formed, while those that originated opposite the polar body tended to become proximal. It follows that, in normal development, bilateral symmetry of the mouse blastocyst anticipates the polarity of the later conceptus. Moreover, our results show that transformation of the blastocyst axis of symmetry into the axes of the postimplantation conceptus involves asymmetric visceral endoderm cell movement. Therefore, even if the definitive axes of the mouse embryo become irreversibly established only after implantation, this polarity can be traced back to events before implantation.
Graded interference with FGF signalling reveals its dorsoventral asymmetry at the mid-hindbrain boundary
Authors: Carl Matthias , Wittbrodt Joachim 
Published: April 2021

Abstract
Signalling by fibroblast growth factors (FGFs) at the mid-hindbrain boundary (MHB) is of central importance for anteroposterior neural patterning from the isthmic organiser. Graded suppression of FGF signalling by increasing amounts of a dominant negative FGF receptor provides evidence that in addition to anteroposterior patterning, FGF signalling is also involved in patterning along the dorsoventral axis at the MHB. FGF signalling at the MHB is required for the activation of the HH target gene spalt at the MHB. Our results indicate that FGF signalling mediates the competence of the MHB to activate spalt in response to SHH. This interdependence of the two signalling pathways is also found in the outbudding optic vesicle where HH requires functional FGF signalling to activate spalt in the proximal eye region.
Extensive zygotic control of the anteroposterior axis in the wasp Nasonia vitripennis
Authors: Pultz Mary Anne , Pitt Jason N. , Alto Neal M. 
Published: April 2021

Abstract
Insect axis formation is best understood in Drosophila melanogaster, where rapid anteroposterior patterning of zygotic determinants is directed by maternal gene products. The earliest zygotic control is by gap genes, which determine regions of several contiguous segments and are largely conserved in insects. We have asked genetically whether early zygotic patterning genes control similar anteroposterior domains in the parasitoid wasp Nasonia vitripennis as in Drosophila. Nasonia is advantageous for identifying and studying recessive zygotic lethal mutations because unfertilized eggs develop as males while fertilized eggs develop as females. Here we describe recessive zygotic mutations identifying three Nasonia genes: head only mutant embryos have posterior defects, resembling loss of both maternal and zygotic Drosophila caudal function; headless mutant embryos have anterior and posterior gap defects, resembling loss of both maternal and zygotic Drosophila hunchback function; squiggy mutant embryos develop only four full trunk segments, a phenotype more severe than those caused by lack of Drosophila maternal or zygotic terminal gene functions. These results indicate greater dependence on the zygotic genome to control early patterning in Nasonia than in the fly.
Genetic control of programmed cell death in the Caenorhabditis elegans hermaphrodite germline
Authors: Gumienny Tina L. , Lambie Eric , Hartwieg Erika , Horvitz H. Robert , Hengartner Michael O. 
Published: April 2021

Abstract
Development of the nematode Caenorhabditis elegans is highly reproducible and the fate of every somatic cell has been reported. We describe here a previously uncharacterized cell fate in C. elegans: we show that germ cells, which in hermaphrodites can differentiate into sperm and oocytes, also undergo apoptotic cell death. In adult hermaphrodites, over 300 germ cells die, using the same apoptotic execution machinery (ced-3, ced-4 and ced-9) as the previously described 131 somatic cell deaths. However, this machinery is activated by a distinct pathway, as loss of egl-1 function, which inhibits somatic cell death, does not affect germ cell apoptosis. Germ cell death requires ras/MAPK pathway activation and is used to maintain germline homeostasis. We suggest that apoptosis eliminates excess germ cells that acted as nurse cells to provide cytoplasmic components to maturing oocytes.
Neurotransmitter receptor activation triggers p27Kip1 and p21CIP1 accumulation and G1 cell cycle arrest in oligodendrocyte progenitors
Authors: Ghiani Cristina A. , Eisen Alex M. , Yuan Xiaoqing , DePinho Ronald A. , McBain Chris J. , Gallo Vittorio 
Published: April 2021

Abstract
We examined the pathways that link neurotransmitter receptor activation and cell cycle arrest in oligodendrocyte progenitors. We had previously demonstrated that glutamate receptor activation inhibits oligodendrocyte progenitor proliferation and lineage progression. Here, using purified oligodendrocyte progenitors and cerebellar slice cultures, we show that norepinephrine and the β-adrenergic receptor agonist isoproterenol also inhibited the proliferation, but in contrast to glutamate, isoproterenol stimulated progenitor lineage progression, as determined by O4 and O1 antibody staining. This antiproliferative effect was specifically attributable to a β-adrenoceptormediated increase in cyclic adenosine monophosphate, since analogs of this cyclic nucleotide mimicked the effects of isoproterenol on oligodendrocyte progenitor proliferation, while α-adrenoceptor agonists were ineffective. Despite the opposite effects on lineage progression, both isoproterenol and the glutamate receptor agonist kainate caused accumulation of the cyclindependent kinase inhibitors p27Kip1 and p21CIP1, and G1 arrest. Studies with oligodendrocyte progenitor cells from INK4a–/– mice indicated that the G1 cyclin kinase inhibitor p16INK4a as well as p19ARF were not required for agoniststimulated proliferation arrest. Our results demonstrate that β-adrenergic and glutamatergic receptor activation inhibit oligodendrocyte progenitor proliferation through a mechanism that may involve p27Kip1 and p21CIP1; but while neurotransmitter-induced accumulation of p27Kip1 is associated with cell cycle arrest, it does not by itself promote oligodendrocyte progenitor differentiation.
Similarity of DNA binding and transcriptional regulation by Caenorhabditis elegans MAB-3 and Drosophila melanogaster DSX suggests conservation of sex determining mechanisms
Authors: Yi Woelsung , Zarkower David 
Published: April 2021

Abstract
Although most animals occur in two sexes, the molecular pathways they employ to control sexual development vary considerably. The only known molecular similarity between phyla in sex determination is between two genes, mab-3 from C. elegans, and doublesex (dsx) from Drosophila. Both genes contain a DNA binding motif called a DM domain and they regulate similar aspects of sexual development, including yolk protein synthesis and peripheral nervous system differentiation. Here we show that MAB-3, like the DSX proteins, is a direct regulator of yolk protein gene transcription. We show that despite containing different numbers of DM domains MAB-3 and DSX bind to similar DNA sequences. mab-3 mutations deregulate vitellogenin synthesis at the level of transcription, resulting in expression in both sexes, and the vitellogenin genes have potential MAB-3 binding sites upstream of their transcriptional start sites. MAB-3 binds to a site in the vit-2 promoter in vitro, and this site is required in vivo to prevent transcription of a vit-2 reporter construct in males, suggesting that MAB-3 is a direct repressor of vitellogenin transcription. This is the first direct link between the sex determination regulatory pathway and sex-specific structural genes in C. elegans, and it suggests that nematodes and insects use at least some of the same mechanisms to control sexual development.
Induction of the epibranchial placodes
Authors: Begbie Jo , Brunet Jean-Francois , Rubenstein John L. R. , Graham Anthony 
Published: April 2021

Abstract
The cranial sensory ganglia, in contrast to those of the trunk, have a dual embryonic origin arising from both neurogenic placodes and neural crest. Neurogenic placodes are focal thickenings of ectoderm, found exclusively in the head of vertebrate embryos. These structures can be split into two groups based on the positions that they occupy within the embryo, dorsolateral and epibranchial. The dorsolateral placodes develop alongside the central nervous system, while the epibranchial placodes are located close to the top of the clefts between the branchial arches. Importantly, previous studies have shown that the neurogenic placodes form under the influence of the surrounding cranial tissues. In this paper, we have analysed the nature of the inductive signal underlying the formation of the epibranchial placodes. We find that epibranchial placodes do not require neural crest for their induction, but rather that it is the pharyngeal endoderm that is the source of the inductive signal. We also find that, while cranial ectoderm is competent to respond to this inductive signal, trunk ectoderm is not. We have further identified the signalling molecule Bmp7 as the mediator of this inductive interaction. This molecule is expressed in a manner consistent with it playing such a role and, when added to ectoderm explants, it will promote the formation of epibranchial neuronal cells. Moreover, the Bmp7 antagonist follstatin will block the ability of pharyngeal endoderm to induce placodal neuronal cells, demonstrating that Bmp7 is required for this inductive interaction. This work answers the long standing question regarding the induction of the epibranchial placodes, and represents the first elucidation of an inductive mechanism, and a molecular effector, underlying the formation of any primary sensory neurons in higher vertebrates.
Delta1 expression during avian hair cell regeneration
Authors: Stone Jennifer S. , Rubel Edwin W. 
Published: April 2021

Abstract
Postembryonic production of hair cells, the highly specialized receptors for hearing, balance and motion detection, occurs in a precisely controlled manner in select species, including avians. Notch1, Delta1 and Serrate1 mediate cell specification in several tissues and species. We examined expression of the chicken homologs of these genes in the normal and drug-damaged chick inner ear to determine if signaling through this pathway changes during hair cell regeneration. In untreated post-hatch chicks, Delta1 mRNA is abundant in a subpopulation of cells in the utricle, which undergoes continual postembryonic hair cell production, but it is absent from all cells in the basilar papilla, which is mitotically quiescent. By 3 days after drug-induced hair cell injury, Delta1 expression is highly upregulated in areas of cell proliferation in both the utricle and basilar papilla. Delta1 mRNA levels are elevated in progenitor cells during DNA synthesis and/or gap 2 phases of the cell cycle and expression is maintained in both daughter cells immediately after mitosis. Delta1 expression remains upregulated in cells that differentiate into hair cells and is downregulated in cells that do not acquire the hair cell fate. Delta1 mRNA levels return to normal by 10 days after hair cell injury. Serrate1 is expressed in both hair cells and support cells in the utricle and basilar papilla, and its expression does not change during the course of drug-induced hair cell regeneration. In contrast, Notch1 expression, which is limited to support cells in the quiescent epithelium, is increased in post-M-phase cell pairs during hair cell regeneration. This study provides initial evidence that Delta-Notch signaling may be involved in maintaining the correct cell types and patterns during postembryonic replacement of sensory epithelial cells in the chick inner ear.