bluuebunny/crossref_metadata_2025_split huggingface dataset:
Bax promotes neuronal survival and antagonises the survival effects of neurotrophic factors
Authors: Middleton Gayle , Nunez Gabriel , Davies Alun M. 
Published: April 2021

ABSTRACT
Bcl-2, Bcl-x and Bax are members of a family of cytoplasmic proteins that influence cell survival. Whereas increased expression of Bcl-2 or Bcl-x promotes cell survival following withdrawal of survival factors, increased expression of Bax is thought to suppress survival. To investigate the potential roles of these proteins in regulating the survival of developing neurons, we compared the effects of overexpressing these proteins in embryonic neurons deprived of different neurotrophic factors in vitro. Surprisingly, overexpression of Bax rescued populations of sensory neurons deprived of nerve growth factor, as did overexpression of Bcl-2 and two Bcl-x variants, Bcl-xL and Bcl-xβ. Bax also enhanced the survival of ciliary neurons deprived of ciliary neurotrophic factor, although this effect was short-lived. Whereas Bcl-2 overexpression did not affect the survival response of neurons to neurotrophic factors, Bax overexpression partially inhibited the action of neurotrophic factors. Co-injection of Bcl-2 and Bax expression vectors promoted the survival of neurotrophic factor-deprived neurons if either was in excess, but failed to rescue neurons if they were injected at a 1:1 ratio. Our findings demonstrate that Bax can promote the survival of neurotrophic factor-deprived neurons and that its effect on survival is dominant to that of neurotrophic factors. Our results also argue that the relative amounts of Bcl-2 and Bax are critical in regulating neuronal survival.
Drosophila Paired regulates late even-skipped expression through a composite binding site for the paired domain and the homeodomain
Authors: Fujioka Miki , Miskiewicz Pawel , Raj Lakshmi , Gulledge Alyssa A. , Weir Michael , Goto Tadaatsu 
Published: April 2021

ABSTRACT
The even-skipped (eve) pair-rule gene plays a key role in the establishment of the anterior-posterior segmental pattern of the Drosophila embryo. The continuously changing pattern of eve expression can be resolved into two phases. Early expression consists of seven broad stripes in the blastoderm embryo, while late expression, which occurs after cellularization, consists of narrow stripes with sharp anterior borders that coincide with the odd-numbered parasegment boundaries. Previous studies have shown that these two phases are controlled by separate classes of cis elements in the eve promoter. Early stripes are expressed by multiple stripe-specific elements under the control of maternal-effect genes and gap genes, while late stripes are expressed by a single regulatory element, the ‘late element’, under the control of pair-rule genes including eve itself. We report here that paired (prd), a pair-rule gene which had been considered to be below eve in the regulatory hierarchy of pair-rule genes, in fact plays a critical role in the regulation of late eve expression. Transgenic analysis shows that this regulation is largely mediated by an evolutionarily conserved sequence within the late element termed PTE (Paired Target Element). In vitro analysis shows that the Prd protein binds strongly to this sequence. Interestingly, PTE contains juxtaposed binding sites for the two DNAbinding domains of the Prd protein, the paired domain and the homeodomain. Mutagenesis of either binding site leads to significant reduction in the activity of the late element, indicating that both DNA-binding domains in the Paired protein are required for regulation.
Functional relationships between Notch, Su(H) and the bHLH genes of the E(spl) complex: the E(spl) genes mediate only a subset of Notch activities during imaginal development
Authors: de Celis Jose F. , Celis Jesus de , Ligoxygakis Petros , Preiss Anette , Delidakis Christos , Bray Sarah 
Published: April 2021

ABSTRACT
The basic helix-loop-helix proteins of the Enhancer of split complex constitute a link between activation of the transmembrane receptor Notch and the resulting effects on transcription of downstream genes. The Suppressor of Hairless protein is the intermediary between Notch activation and expression of all Enhancer of split genes even though individual genes have distinct patterns of expression in imaginal discs. A comparison between the phenotypes produced by Notch, Suppressor of Hairless and Enhancer of split mutations in the wing and thorax indicate that Suppressor of Hairless and Notch requirements are indistinguishable, but that Enhancer of split activity is only essential for a subset of developmental processes involving Notch function. Likewise, the ectopic expression of Enhancer of split proteins does not reproduce all the consequences typical of ectopic Notch activation. We suggest that the Notch pathway bifurcates after the activation of Suppressor of Hairless and that Enhancer of split activity is not required when the consequence of Notch function is the transcriptional activation of downstream genes. Transcriptional activation mediated by Suppressor of Hairless and transcriptional repression mediated by Enhancer of split could provide greater diversity in the response of individual genes to Notch activity.
Evidence that MSL-mediated dosage compensation in Drosophila begins at blastoderm
Authors: Franke Axel , Dernburg Abby , Bashaw Greg J. , Baker Bruce S. 
Published: April 2021

ABSTRACT
In Drosophila equalization of the amounts of gene products produced by X-linked genes in the two sexes is achieved by hypertranscription of the single male X chromosome. This process, dosage compensation, is controlled by a set of male-specific lethal (msl) genes, that appear to act at the level of chromatin structure. The properties of the MSL proteins have been extensively studied in the polytene salivary gland chromosomes where they bind to the same set of sites along the male X chromosome in a co-dependent manner. Here we report experiments that show that the MSL proteins first associate with the male X chromosome as early as blastoderm stage, slightly earlier than the histone H4 isoform acetylated at lysine 16 is detected on the X chromosome. MSL binding to the male X chromosome is observed in all somatic tissues of embryos and larvae. Binding of the MSLs to the X chromosome is also interdependent in male embryos and prevented in female embryos by the expression of Sex-lethal (Sxl). A delayed onset of binding of the MSLs in male progeny of homozygous mutant msl-1 or mle mothers coupled with the previous finding that such males have an earlier lethal phase supports the idea that msl-mediated dosage compensation begins early in embryogenesis. Other results show that the maleless (MLE) protein on embryo and larval chromosomes differs in its reactivity with antibodies; the functional significance of this finding remains to be explored.
Identification of a novel cardiac-specific transcript critical for cardiac myocyte differentiation
Authors: Wei Yan , Bader David , Litvin Judith 
Published: April 2021

ABSTRACT
A novel cDNA, pCMF1, which is expressed exclusively and transiently in the myogenic cells of the differentiating chicken heart was isolated and characterized. The fulllength cDNA of pCMF1 has one open reading frame encoding 1538 predicted amino acids. While computer analysis predicts the presence of specific structural motifs, the overall sequence of pCMF1 is unique. The pattern of pCMF1 gene expression during heart formation was determined by whole-mount in situ hybridization. pCMF1 is transiently expressed within the myogenic cells of the primitive heart tube from stages 9 to 18 and is not detected in the heart or any other tissue thereafter. A replicationdeficient retrovirus was used to mediate pCMF1 antisense expression in cardiogenic mesoderm. These analyses determined that the presence of pCMF1 antisense sequences disrupted myosin heavy chain expression during cardiac mesoderm differentiation. pCMF1 antisense had no effect on myosin heavy chain expression in differentiated cardiac myocytes. These data suggest a potential function for pCMF1 during cardiac myogenesis.
wingless signaling in the Drosophila eye and embryonic epidermis
Authors: Cadigan Kenneth M. , Nusse Roel 
Published: April 2021

ABSTRACT
After the onset of pupation, sensory organ precursors, the progenitors of the interommatidial bristles, are selected in the developing Drosophila eye. We have found that wingless, when expressed ectopically in the eye via the sevenless promoter, blocks this process. Transgenic eyes have reduced expression of acheate, suggesting that wingless acts at the level of the proneural genes to block bristle development. This is in contrast to the wing, where wingless positively regulates acheate to promote bristle formation. The sevenless promoter is not active in the acheate-positive cells, indicating that the wingless is acting in a paracrine manner. Clonal analysis revealed a requirement for the genes porcupine, dishevelled and armadillo in mediating the wingless effect. Overexpression of zeste white-3 partially blocks the ability of wingless to inhibit bristle formation, consistent with the notion that wingless acts in opposition to zeste white-3. Thus the wingless signaling pathway in the eye appears to be very similar to that described in the embryo and wing. The Notch gene product has also been suggested to play a role in wingless signaling (J. P. Couso and A. M. Martinez Arias (1994)Cell 79, 259–72). Because Notch has many functions during eye development, including its role in inhibiting bristle formation through the neurogenic pathway, it is difficult to assess the relationship of Notch to wingless in the eye. However, we present evidence that wingless signaling still occurs normally in the complete absence of Notch protein in the embryonic epidermis. Thus, in the simplest model for wingless signalling, a direct role for Notch is unlikely.
Coordination of early neural tube development by BDNF/trkB
Authors: Jungbluth Stefan , Koentges Georgy , Lumsden Andrew 
Published: April 2021

ABSTRACT
Neurotrophins signal through members of the trk family of tyrosine kinase receptors and are known to regulate several neuronal properties. Although initially characterized by their ability to prevent naturally occurring cell death of subsets of neurons during development, neurotrophins can also regulate the proliferation and differentiation of precursor cells. Here we report a novel involvement of neurotrophins in early development of the neural tube. We demonstrate that a functional trkB receptor is expressed by motor neuron progenitors in the ventral neural tube and that treatment of ventral neural tube explants with the trkB ligand Brain-Derived Neurotrophic Factor (BDNF) leads to a significant increase in the number of motor neurons. The only BDNF expression detectable at this stage is by a subset of ventrally projecting interneurons in the dorsal neural tube; ablating this region in vivo leads to a reduction of motor neuron numbers. This loss can be prevented by simultaneous treatment with BDNF. We propose that BDNF produced by dorsal interneurons stimulates proliferation and/or differentiation of motor neuron progenitors after anterograde axonal transport and release in proximity to the trkB-expressing motor neuron precursors, thereby coordinating development between dorsal and ventral regions of the neural tube.
Differential expression of mammalian Numb, Numblike and Notch1 suggests distinct roles during mouse cortical neurogenesis
Authors: Zhong Weimin , Jiang Ming-Ming , Weinmaster Gerry , Jan Lily Yeh , Jan Yuh Nung 
Published: April 2021

ABSTRACT
During Drosophila neurogenesis, asymmetric cell divisions are achieved by differential segregation of Numb (d-Numb) into one of the daughter cells to cause a bias in the Notch mediated cell-cell interaction. We have isolated a second mammalian gene with significant sequence similarity tod-numb, mouse numblike. When expressed in dividing neural precursors in Drosophila, Numblike is symmetrically distributed in the cytoplasm, unlike endogenous d-Numb or expressed mouse Numb (m-Numb), both of which are asymmetrically localized to one half of the cell membrane. In d-numb loss-of-function mutant embryos, expression of Numblike allows both daughter cells of a neural precursor to adopt the fate of the cell that normally inherits d-Numb. In mice, numblike mRNA is preferentially expressed in adult and embryonic nervous system. In the developing neocortex, Numblike is expressed in postmitotic neurons in the cortical plate, but not in progenitors within the ventricular zone where m-Numb and Notch1 are expressed. We have also found that, in dividing cortical progenitors, Notch1 is distributed around the entire membrane, unlike m-Numb which is asymmetrically localized to the apical membrane. We propose that an interplay between cell-intrinsic mechanisms (executed by m-numb and numblike) and cell-extrinsic mechanisms (mediated by Notch1) may be involved in both progenitor cell proliferation and neuronal differentiation during mammalian cortical neurogenesis.
Cell fate in the chick limb bud and relationship to gene expression
Authors: Vargesson Neil , Clarke Jonathan D. W. , Vincent Katherine , Coles Clare , Wolpert Lewis , Tickle Cheryll 
Published: April 2021

ABSTRACT
We have produced detailed fate maps for mesenchyme and apical ridge of a stage 20 chick wing bud. The fate maps of the mesenchyme show that most of the wing arises from the posterior half of the bud. Subapical mesenchyme gives rise to digits. Cell populations beneath the ridge in the mid apical region fan out into the anterior tip of the handplate, while posterior cell populations extend right along the posterior margin. Subapical mesenchyme of the leg bud behaves similarly. The absence of anterior bending of posterior cell populations has implications when considering models of vertebrate limb evolution. The fatemaps of the apical ridge show that there is also a marked anterior expansion and cells that were in anterior apical ridge later become incorporated into non-ridge ectoderm along the margin of the bud. Mesenchyme and apical ridge do not expand in concert - the apical ridge extends more anteriorly. We used the fatemaps to investigate the relation-ship between cell lineage and elaboration of Hoxd-13 and Fgf-4 domains. Hoxd-13 and Fgf-4 are initially expressed posteriorly until about the mid-point of the early wing bud in mesenchyme and apical ridge respectively. Later in development, the genes come to be expressed throughout most of the handplate and apical ridge respectively. We found that at the proximal edge of the Hoxd-13 domain, cell populations stopped expressing the gene as development proceeded and found no evidence that the changes in extent of the domains were due to initiation of gene expression in anterior cells. Instead the changes in extent of expression fit with the fate maps and can be attributed to expansion and fanning out of cell populations initially expressing the genes.
Pax-6 functions in boundary formation and axon guidance in the embryonic mouse forebrain
Authors: Mastick Grant S. , Davis Nicole M. , Andrews Gracie L. , Easter Stephen S. 
Published: April 2021

ABSTRACT
The Pax-6 gene encodes a transcription factor that is expressed in regionally restricted patterns in the developing brain and eye. Here we describe Pax-6 expression in the early forebrain (prosencephalon) on embryonic day 9.5 (E9.5) to E10.5 using both whole-mount in situ hybridization and antibody labeling. We find close correlations between Pax-6+ domains and initial neural patterning, and identify corresponding defects in embryos homozygous for the Pax-6 allele, Small eye (Sey). Pax-6 expression defines the prosencephalon-mesencephalon boundary, and mutant embryos lack this morphological boundary. Markers of the caudal prosencephalon are lost (Pax-6, Lim-1, Gsh-1) and a marker for mesencephalon is expanded rostrally into the prosencephalon (Dbx). We conclude that the caudal prosencephalon (prosomere 1) is at least partially transformed to a mesencephalic fate. This transformation results in a specific deficit of posterior commissure axons. Sey/Sey embryos also exhibit an axon pathfinding defect specific to the first longitudinal tract in the prosencephalon (tpoc, tract of the postoptic commissure). In wild type, tpoc axons fan out upon coming in contact with a superficial patch of Pax-6+ neuron cell bodies. In the mutant, the tpoc axons have normal initial projections, but make dramatic errors where they contact the neuron cell bodies, and fail to pioneer this first tract. Thus Pax-6 is required for local navigational information used by axons passing through its domain of expression.
We conclude that Pax-6 plays multiple roles in forebrain patterning, including boundary formation, regional patterning, neuron specification and axon guidance.
Reassessing embryogenesis in the Ctenophora: the inductive role of e1 micromeres in organizing ctene row formation in the ‘mosaic’ embryo, Mnemiopsis leidyi
Authors: Martindale Mark Q. , Henry Jonathan Q. 
Published: April 2021

ABSTRACT
Ctenophores are a phylum of diploblastic marine animals displaying biradial symmetry organized along an oral aboral axis. One of the apomorphic sets of adult structures in ctenophores are the eight external comb rows, which run along the oral-aboral axis. Comb rows consist of serial arrays of individual comb plates of cilia, which beat in a coordinated fashion for locomotory behavior. Classical cell lineage experiments using chalk particles indicated that comb rows are derived exclusively from the four e1 micromeres at the 16-cell stage. This conclusion was also supported by the fact that no ctene rows (or their underly ing endodermal canals) form when all four e1 micromeres were deleted. We have used intracellular diI cell lineage tracing to determine that, in addition to e1 micromeres, the four m1 micromeres also make significant contributions to the ctene rows. Thus, e1 micromere derivatives not only generate comb plates but are required for ctene row formation by m1 derivatives. These results demonstrate that inductive interactions are an important component of early development in ctenophores and indicate that e1 micromeres influence the development of adjacent cell lineages (both m1 and endodermal lineages) during ctenophore embryogenesis. In addition, intracellular labeling has revealed that there are subtle variations in the composition of clones derived from identified embryonic blastomeres. Together these findings reveal a picture of ctenophore embryogenesis, which is in marked contrast to the former rigid ‘mosaic’ reputation of ctenophore devel opment, and invite speculation as to the role of the cleavage program in embryonic patterning in the lower Metazoa.
Tight junction assembly during mouse blastocyst formation is regulated by late expression of ZO-1 α+ isoform
Authors: Sheth Bhavwanti , Fesenko Ira , Collins Jane E. , Moran Breda , Wild Arthur E. , Anderson James M. , Fleming Tom P. 
Published: April 2021

ABSTRACT
The mouse preimplantation embryo has been used to investigate the de novo synthesis of tight junctions during trophectoderm epithelial differentiation. We have shown previously that individual components of the tight junction assemble in a temporal sequence, with membrane assembly of the cytoplasmic plaque protein ZO-1 occurring 12 hours before that of cingulin. Subsequently, two alternatively spliced isoforms of ZO-1 (α+ and α−), differing in the presence or absence of an 80 residue α domain were reported. Here, the temporal and spatial expression of these ZO-1 isoforms has been investigated at different stages of preimplantation development. ZO-1α−mRNA was present in oocytes and all preimplantation stages, whilst ZO-1α +transcripts were first detected in embryos at the morula stage, close to the time of blastocoele formation. mRNAs for both isoforms were detected in trophectoderm and ICM cells. Immunoprecipitation of 33S-labelled embryos also showed synthesis of ZO-1α − throughout cleavage, whereas synthesis of ZO-1α +was only apparent from the blastocyst stage. In addition, 33P-labelling showed both isoforms to be phosphorylated at the early blastocyst stage. The pattern and timing of membrane assembly of the two isoforms was also distinct. ZO-1α− was initially seen as punctate sites at the cell-cell contacts of compact 8-cell embryos. These sites then coalesced laterally along the
membrane until they completely surrounded each cell with a zonular belt by the late morula stage. ZO-1α +however, was first seen as perinuclear foci in late morulae before assembling at the tight junction. Membrane assembly of ZO-1α +first occurred during the 32-cell stage and was zonular just prior to the early blastocyst stage. Immunostaining indicative of both isoforms was restricted to the trophectoderm lineage. Membrane assembly of ZO-1α +and blastocoele formation were sensitive to brefeldin A, an inhibitor of intracellular trafficking beyond the Golgi complex. In addition, the tight junction transmembrane protein occludin co-localised with ZO-1α +at the perinuclear sites in late morulae and at the newly assembled cell junctions. These results provide direct evidence from a native epithelium that ZO-1 isoforms perform distinct roles in tight junction assembly. Moreover, the late expression of ZO-1α +and its apparent intracellular interaction with occludin may act as a final rate-limiting step in the synthesis of the tight junction, thereby regulating the time of junction sealing and blastocoele formation in the early embryo.
Müller-cell-derived leukaemia inhibitory factor arrests rod photoreceptor differentiation at a postmitotic pre-rod stage of development
Authors: Neophytou Costas , Vernallis Ann B. , Smith Austin , Raff Martin C. 
Published: April 2021

ABSTRACT
In the present study, we examine rod photoreceptor development in dissociated-cell cultures of neonatal mouse retina. We show that, although very few rhodopsin+ rods develop in the presence of 10% foetal calf serum (FCS), large numbers develop in the absence of serum, but only if the cell density in the cultures is high. The rods all develop from nondividing rhodopsin−cells, and new rods continue to develop from rhodopsin− cells for at least 6-8 days, indicating that there can be a long delay between when a precursor cell withdraws from the cell cycle and when it becomes a rhodopsin+ rod. We show that FCS arrests rod development in these cultures at a postmitotic, rhodopsin−, pre-rod stage. We present evidence that FCS acts indirectly by stimulating the proliferation of Müller cells, which arrest rod differentiation by releasing leukaemia inhibitory factor (LIF). These findings identify an inhibitory cell-cell interaction, which may help to explain the long delay that can occur both in vitro and in vivo between cell-cycle withdrawal and rhodopsin expression during rod development.