bluuebunny/crossref_metadata_2025_split huggingface dataset:
extradenticle determines segmental identities throughout Drosophila development
Authors: Rauskolb Cordelia , Smith Katherine M. , Peifer Mark , Wieschaus Eric 
Published: April 2021

ABSTRACT
extradenticle (exd) and the homeotic selector proteins together establish segmental identities by coordinately regulating the expression of downstream target genes. The inappropriate expression of these targets in exd mutant embryos results in homeotic transformations and aberrant morphogenesis. Here we examine the role of exd in adult development by using genetic mosaics and a hypomorphic exd allele caused by a point mutation in the homeodomain. exd continues to be essential for the specification of segmental identities, consistent with a continuing requirement for exd as a cofactor of the homeotic selector proteins. Loss of exd results in the homeotic transformation of abdominal segments to an A5 or A6 segmental identity, the antenna and arista to leg, and the head capsule to dorsal thorax or notum. Proximal leg structures are particularly sensitive to the loss of exd, although exd does not affect the allocation of proximal positional values of the leg imaginal disc. Using heat-shocks to induce expression of a hsp70-exd fusion gene, we show that, in contrast to the homeotic selector genes, ubiquitously high levels of exd expression do not cause pattern abnormalities or segmental transformations.
Myogenesis in paraxial mesoderm: preferential induction by dorsal neural tube and by cells expressing Wnt-1
Authors: Stern Howard M. , Brown Anthony M. C. , Hauschka Stephen D. 
Published: April 2021

ABSTRACT
Previous studies have demonstrated that the neural tube/notochord complex is required for skeletal muscle development within somites. In order to explore the localization of myogenic inducing signals within the neural tube, dorsal or ventral neural tube halves were cultured in contact with single somites or pieces of segmental plate mesoderm. Somites and segmental plates cultured with the dorsal half of the neural tube exhibited 70% and 85% myogenic response rates, as determined by immunostaining for myosin heavy chain. This response was slightly lower than the 100% response to whole neural tube/notochord, but was much greater than the 30% and 10% myogenic response to ventral neural tube with and without notochord. These results demonstrate that the dorsal neural tube emits a potent myogenic inducing signal which accounts for most of the inductive activity of whole neural tube/notochord. However, a role for ventral neural tube/notochord in somite myogenic induction was clearly evident from the larger number of myogenic cells induced when both dorsal neural tube and ventral neural tube/notochord were present. To address the role of a specific dorsal neural tube factor in somite myogenic induction, we tested the ability of Wnt-1-expressing fibroblasts to promote paraxial mesoderm myogenesis in vitro. We found that cells expressing Wnt-1 induced a small number of somite and segmental plate cells to undergo myogenesis. This finding is consistent with the localized dorsal neural tube inductive activity described above, but since the ventral neural tube/notochord also possesses myogenic inductive capacity yet does not express Wnt-1, additional inductive factors are likely involved.
Cell fate specification by even-skipped expression in the Drosophila nervous system is coupled to cell cycle progression
Authors: Weigmann Katrin , Lehner Christian F. 
Published: April 2021

ABSTRACT
The correct specification of defined neurons in the Drosophila central nervous system is dependent on evenskipped. During CNS development, even-skipped expression starts in the ganglion mother cell resulting from the first asymmetric division of neuroblast NB 1-1. This first division of NB 1-1 (and of the other early neuroblasts as well) is temporally controlled by the transcriptional regulation of string expression, which we have manipulated experimentally. even-skipped expression still occurs if the first neuroblast division is delayed, but not if the division is prohibited. Moreover, even-skipped expression is also dependent on progression through S phase which follows immediately after the first division. However, cytokinesis during the first NB division is not required for even-skipped expression as revealed by observations in pebble mutant embryos. Our results demonstrate therefore that evenskipped expression is coupled to cell cycle progression, presumably in order to prevent a premature activation of expression by a positive regulator which is produced already in the neuroblast during G2 and segregated asymmetrically into the ganglion mother cell during mitosis.
Synthesis and release of 9-cis retinoic acid by the urodele wound epidermis
Authors: Viviano Carolyn M. , Horton Claire E. , Maden Malcolm , Brockes Jeremy P. 
Published: April 2021

ABSTRACT
The wound epidermis is a transient secretory epithelium that apposes the mesenchymal blastema of a regenerating urodele limb, and is required for regeneration. Previous studies have shown that the positional identity of the blastema is respecified by retinoic acid (RA; Maden, M. (1982)Nature 295, 672-675), that the blastema contains RA (Scadding, S. R. and Maden, M. (1994) Dev. Biol. 162, 608617), and that an RA-reporter gene introduced into the blastema is differentially activated along the proximodistal axis (Brockes, J. P. (1992)Proc. Natl. Acad. Sci. USA 89, 11386-11390). The newt limb wound epidermis has been explanted with minimal mesenchymal contamination and cultured under conditions where it retains expression and inducibility of marker antigens. We have assayed for the release of retinoids from the wound epidermis by coculture with cells transfected with an RA-responsive reporter gene. The reporter was activated to a level corresponding to stimulation by 0.1–1 nM RA, and this activation was substantially conferred by medium conditioned by the wound epidermis. No significant activation was observed for cells transfected with mutated reporter plasmids and analysed in parallel co-cultures. Wound epidermis from contralateral proximal and distal blastemas were compared for reporter activation, and gave a P/D activation ratio significantly greater than 1.Wound epidermis explants were cultured in the presence of tritiated retinol, and extracts were analysed by HPLC on three different columns. Radioactivity was detected in peaks corresponding to didehydroretinol, 9-cis RA and other unidentified metabolites. Analysis of conditioned media samples, some after pulse chase experiments, detected significant release of retinol, 9-cis RA and other metabolites. Although all-trans RA was detectable, the predominant acidic metabolite was 9-cis RA. These experiments establish the wound epidermis as a source of RA for local cellular interactions in the blastema.
The homeobox-containing gene XANF-1 may control development of the Spemann organizer
Authors: Zaraisky A. G. , Ecochard V. , Kazanskaya O. V. , Lukyanov S. A. , Fesenko I. V. , Duprat A.-M. 
Published: April 2021

ABSTRACT
At the beginning of gastrulation the homeobox-containing gene, XANF-1, is expressed at a low level throughout the animal hemisphere of Xenopus laevis embryos, with a local maximum of expression in the region of the dorsal blastopore lip. By the end of gastrulation expression ceases everywhere except in the most anterior part of the neurectoderm. We have investigated the functions of this gene by microinjecting XANF-1 mRNA in the blastomeres of the 32-cell stage embryo and have observed the following effects. First, microinjections of the mRNA in the animal blastomeres and the blastomeres of the marginal zone elicited massive migration of cells to the interior of the embryo at the early gastrula stage. Second, overexpression of XANF-1 in the ventral marginal zone (VMZ) resulted in the appearance of an additional centre of gastrulation movements and the formation of a secondary axis. In addition we showed that synthetic XANF-1 mRNA was able to cause dorsal-type differentiation in VMZ explants extirpated from the microinjected embryos at the beginning of gastrulation. These results suggest that XANF-1 may control the main functions of cells of the Spemann organizer.
Embryonic development of the Drosophila brain: formation of commissural and descending pathways
Authors: Therianos Stavros , Leuzinger Sandra , Hirth Frank , Goodman Corey S. , Reichert Heinrich 
Published: April 2021

ABSTRACT
The establishment of initial axonal pathways in the embryonic brain of Drosophila melanogaster was investigated at the cellular and molecular level using antibody probes, enhancer detector strains and axonal pathfinding mutants. During embryogenesis, two bilaterally symmetrical cephalic neurogenic regions form, which are initially separated from each other and from the ventral nerve cord. The brain commissure that interconnects the two brain hemispheres is pioneered by axons that project towards the midline in close association with an interhemispheric cellular bridge. The descending longitudinal pathways that interconnect the brain to the ventral nerve cord are prefigured by a chain of longitudinal glial cells and a cellular bridge between brain and subesophageal ganglion; pioneering descending and ascending neurons grow in close association with these structures. The formation of the embryonic commissural and longitudinal pathways is dependent on cells of the CNS midline. Mutations in the commissureless gene, which affects growth cone guidance towards the midline, result in a marked reduction of the brain commissure. Mutations in the single-minded gene and in other spitz group genes, which affect the differentiation of CNS midline cells, result in the absence or aberrant projection of longitudinal pathways. The analysis of axon pathway formation presented here reveals remarkable similarities as well as distinct differences in the embryonic development of the brain and the segmental ganglia, and forms the basis for a comprehensive genetic and molecular genetic dissection of axonal pathfinding processes in the developing brain.
Differential regulation of AP-1 and novel TRE-specific DNA-binding complexes during differentiation of oligodendrocyte-type-2-astrocyte (O-2A) progenitor cells
Authors: Barnett Susan C. , Rosario Marta , Doyle Arthur , Kilbey Anna , Lovatt Archie , Gillespie David A. F. 
Published: April 2021

ABSTRACT
AP-1 is an ubiquitous transcription factor which is composed of the Jun and Fos proto-oncogene proteins and is thought to play a role in both cell proliferation and differentiation. We have used an immortal, bipotential oligodendrocyte-type-2 astrocyte progenitor cell line (O-2A/c-myc) which can differentiate into oligodendrocytes or type-2 astrocytes in vitro, to investigate whether AP-1 DNA-binding activity fluctuates during glial cell differentiation. Unexpectedly, DNA-mobility shift assays using a TRE-containing oligonucleotide derived from the promoter of the glial-specific gene, glial fibrillary acidic protein (GFAP/AP-1), revealed that O-2A/c-myc progenitor cells were devoid of conventional AP-1 DNA-binding complexes. O-2A/c-myc cells did however contain several novel GFAP/AP-1-specific DNA-binding complexes, which we have termed APprog. APprog complexes recognise the TRE consensus motif present in the GFAP/AP-1 oligonucleotide together with adjacent 3′ sequences but do not contain c-Jun or any other known Jun-related proteins. When O-2A/c-myc cells underwent terminal differentiation APprog complexes were lost and conventional AP-1 DNA-binding activity became evident, particularly in astrocytes. These changes appear to be closely linked to the differentiation process since they did not occur in a derivative of the O-2A/c-myc cell line that contains an activated v-ras oncogene and which fails to differentiate under appropriate culture conditions. The inverse regulation of conventional AP-1 and APprog complexes within the O-2A lineage suggests that these factors may play a role in the regulation of glial cell differentiation or glial cell-specific gene expression.
dishevelled is a component of the frizzled signaling pathway in Drosophila
Authors: Krasnow Randi E. , Wong Lily L. , Adler Paul N. 
Published: April 2021

ABSTRACT
The tissue polarity genes in Drosophila are required to coordinate cell polarity within the plane of the epidermis. Evidence to date suggests that these genes may encode components of a novel signal transduction pathway. Three of the genes, frizzled (fz), dishevelled (dsh), and prickle (pk) share a similar tissue polarity phenotype, suggesting that they function together in a single process. dsh is also known to function as a mediator of wingless (wg) signaling in a variety of developmental patterning processes in the fly. In this study, we make use of a fz transgene and a hypomorphic fz allele as genetic tools in an attempt to order these genes in a genetic hierarchy. Our results argue that dsh encodes a dosage sensitive component required for fz function and that it likely acts downstream of fz in the generation of tissue polarity. Our findings suggest that dsh may have a general role in signal transduction, perhaps as a component of a receptor complex.
The expression of the Athb-8 homeobox gene is restricted to provascular cells in Arabidopsis thaliana
Authors: Baima Simona , Nobili Fabio , Sessa Giovanna , Lucchetti Sabrina , Ruberti Ida , Morelli Giorgio 
Published: April 2021

ABSTRACT
We have characterized an Arabidopsis homeobox gene coding for a putative DNA binding protein that represents an early marker for vascular development. The full-length cDNA encodes a protein of 833 amino acids that we have designated Athb-8; it contains the conserved DNA binding domain that characterizes the HD-Zip family of transcription factors. RNA analysis showed that the Athb-8 gene is expressed during the vegetative and the reproductive phases of plant growth. A higher steady-state level of the Athb-8 mRNA was found in flowering stem and root. In situ mRNA analysis of Arabidopsis plants demonstrated that Athb-8 expression is restricted to the procambial cells of embryo and developing organs. Moreover, Athb-8-GUS expression was found in single parenchyma cells which are differentiating into tracheary elements in wounded tobacco transgenic plants. Finally, we showed that the auxin, indole-3-acetic acid, which is involved in vascular development and differentiation, modulates the expression of the gene. Taken together, these results suggest that Athb-8 might be a regulator of vascular development in Arabidopsis thaliana.
The limb deformity mutation disrupts the SHH/FGF-4 feedback loop and regulation of 5′ HoxD genes during limb pattern formation
Authors: Haramis Anna G. , Brown Jennifer M. , Zeller Rolf 
Published: April 2021

ABSTRACT
Mutations in the murine limb deformity (ld) gene disrupt differentiation of the Apical Ectodermal Ridge (AER) and patterning of distal limb structures. However, initial outgrowth of the limb bud is not affected, suggesting that early and late functions of the AER are uncoupled. Similarly, activation of the 5′ members of the HoxD gene cluster (Hoxd-11 to Hoxd-13) is not affected in ld mutant posterior limb bud mesenchyme, but the subsequent anteriorization of 5′ HoxD domains is delayed by about 12 hours and is associated with reduced levels of polarising activity. These results indicate that the ld gene products act upstream of 5′ HoxD genes during patterning of the autopod. Expression of the signalling molecule Sonic hedgehog (Shh) in the posterior limb bud mesenchyme is initiated normally, but ceases prematurely indicating a defect in maintenance of Shh by the ld mutant AER. Fur-thermore, no Fgf-4 transcripts are detected in the ld mutant AER, whereas Fgf-8 transcripts remain expressed. However, Shh expression can be rescued by heterospecific grafting of ld mutant posterior mesenchyme under a wild-type chicken AER. These studies show that the AER defect in ld homozygous limb buds causes disruption of the FGF-4/SHH feedback loop and support the proposed essential role for FGF-4 in maintaining Shh expression during limb pattern formation.
Periaxin expression in myelinating Schwann cells: modulation by axon-glial interactions and polarized localization during development
Authors: Scherer Steven S. , Xu Yi-tian , Bannerman Peter G. C. , Sherman Diane L. , Brophy Peter J. 
Published: April 2021

ABSTRACT
Periaxin is a newly described protein that is expressed exclusively by myelinating Schwann cells. In developing nerves, periaxin is first detected as Schwann cells ensheathe axons, prior to the appearance of the proteins that characterize the myelin sheath. Periaxin is initially concentrated in the adaxonal membrane (apposing the axon) but, during development, as myelin sheaths mature, periaxin becomes predominately localized at the abaxonal Schwann cell membrane (apposing the basal lamina). In permanently axotomized adult nerves, periaxin is lost from the abaxonal and adaxonal membranes, becomes associated with degenerating myelin sheaths and is phagocytosed by macrophages. In crushed nerves, in which axons regenerate and are remyelinated, periaxin is first detected in the adaxonal membrane as Schwann cells ensheathe regenerating axons, but again prior to the appearance of other myelin proteins. Periaxin mRNA and protein levels change in parallel with those of other myelin-related genes after permanent axotomy and crush. These data demonstrate that periaxin is expressed by myelinating Schwann cells in a dynamic, developmentally regulated manner. The shift in localization of periaxin in the Schwann cell after completion of the spiralization phase of myelination suggests that periaxin participates in membrane-protein interactions that are required to stabilize the mature myelin sheath.
Interchangeability of Caenorhabditis elegans DSL proteins and intrinsic signalling activity of their extracellular domains in vivo
Authors: Fitzgerald Kevin , Greenwald Iva 
Published: April 2021

ABSTRACT
Ligands of the Delta/Serrate/lag-2 (DSL) family and their receptors, members of the lin-12/Notch family, mediate cell-cell interactions that specify cell fate in invertebrates and vertebrates. In C. elegans, two DSL genes, lag-2 and apx-1, influence different cell fate decisions during development. Here we show that APX-1 can fully substitute for LAG-2 when expressed under the control of lag-2 regulatory sequences. In addition, we demonstrate that truncated forms lacking the transmembrane and intracellular domains of both LAG-2 and APX-1 can also substitute for endogenous lag-2 activity. Moreover, we provide evidence that these truncated forms are secreted and able to activate LIN-12 and GLP-1 ectopically. Finally, we show that expression of a secreted DSL domain alone may enhance endogenous LAG-2 signalling. Our data suggest ways that activated forms of DSL ligands in other systems may be created.
Anti-Dorsalizing Morphogenetic Protein is a novel TGF-β homolog expressed in the Spemann organizer
Authors: Moos Malcolm , Wang Shouwen , Krinks Marie 
Published: April 2021

ABSTRACT
We have identified a novel growth factor in Xenopus, which is most closely related to human Bone Morphogenetic Protein-3. Its expression peaks during gastrulation, most prominently in the Spemann organizer, and persists in the posterior neural floor plate and prechordal plate during neurulation. Injection of the corresponding mRNA into dorsal blastomeres results in dose-dependent suppression of dorsal and anterior structures, even in the presence of lithium chloride. Overexpression of the gene downregulates the dorsalizing factors noggin, goosecoid and follistatin, as well as the dorsal markers NCAM, muscle actin and MyoD; conversely, ventral markers are induced. We therefore designate this gene product Anti-Dorsalizing Morphogenetic Protein (ADMP). Though development of dorsoanterior structures is suppressed when exogenous ADMP is injected, the gene is induced by lithium chloride treatment or activin, both of which are known to produce the opposite effect. Thus, the expression of ADMP resembles that of several dorsalizing signals, but its product exerts dorsal-suppressing activity. This suggests that ADMP may moderate organizer-associated dorsalizing influences. These findings are also consistent with the recently advanced proposal of dorsally expressed inhibitory activin-like signals.
Segmental patterning of heart precursors in Drosophila
Authors: Lawrence Peter A. , Bodmer Rolf , Vincent Jean-Paul 
Published: April 2021

ABSTRACT
SUMMARY
The mesoderm of Drosophila embryos is segmented; for instance there are segmentally arranged clusters of cells (some of which are heart precursors) that express even-skipped. Expression of even-skipped depends on Wingless, a secreted molecule. In principle, Wingless could act directly in the mesoderm or it could induce the pattern after crossing from ectoderm to mesoderm. Using mosaic embryos, we show that Wingless produced in the mesoderm is sufficient for even-skipped expression. This proves that induction is not essential. However, induction can occur: when patches of wingless mutant mesoderm are overlaid by wild-type ectoderm, they do express even-skipped. We therefore believe that Wingless from both the ectoderm and mesoderm may contribute to patterning the mesoderm. Using the UAS/Gal4 system, we made embryos in which the Wingless protein is uniformly expressed. This is sufficient to rescue the repeated clusters of even-skipped expressing cells, although they are enlarged. We conclude that the mesoderm is segmented in some way not dependent on the distribution of Wingless, suggesting a more permissive and less instructive role for the protein in this instance.
The Caenorhabditis elegans lin-12 gene mediates induction of ventral uterine specialization by the anchor cell
Authors: Newman Anna P. , White John G. , Sternberg Paul W. 
Published: April 2021

ABSTRACT
The anchor cell (AC) of the Caenorhabditis elegans gonad has a critical role in the development of a functional egglaying system, which is accomplished through cell-cell interactions. Lateral inhibitory lin-12-mediated signaling among two bipotential cells causes one to adopt the ventral uterine precursor (VU) cell fate while the other becomes the AC. The AC then induces formation of vulval tissue. We find that the AC also induces a particular ventral uterine intermediate precursor fate (π) by a mechanism that is genetically and temporally distinct from vulval induction. This process requires lin-12, but unlike previously described lin-12-mediated decisions, signaling is unidirectional, is between dissimilar cells and does not involve lateral inhibition. The π fates are necessary for egg laying and appear to produce a distinct specialized cell type. Thus, patterning of the ventral uterus by the AC is crucial to the development of a functional egg-laying system.