Identification of a neurogenic sublineage required for CNS segmentation in an Annelid

Development ◽  
1995 ◽  
Vol 121 (7) ◽  
pp. 2091-2097 ◽  
Author(s):  
F.A. Ramirez ◽  
C.J. Wedeen ◽  
D.K. Stuart ◽  
D. Lans ◽  
D.A. Weisblat
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Embryonic Stem ◽  
Lineage Tracing ◽  
Posterior Edge ◽  
Primary Blast ◽  
Segment Polarity ◽  
Blast Cells ◽  
Segment Polarity Gene ◽  
Polarity Gene

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

Segmentation of the central nervous system in leech

Development ◽  
2000 ◽  
Vol 127 (4) ◽  
pp. 735-744 ◽  
Author(s):  
D.H. Shain ◽  
D.K. Stuart ◽  
F.Z. Huang ◽  
D.A. Weisblat
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Blast Cell ◽  
Cell Behavior ◽  
Present Evidence ◽  
Primary Blast ◽  
Blast Cells ◽  
The Central Nervous System ◽  
Fissure Formation ◽  
The Relationship

Central nervous system (CNS) in leech comprises segmentally iterated progeny derived from five embryonic lineages (M, N, O, P and Q). Segmentation of the leech CNS is characterized by the formation of a series of transverse fissures that subdivide initially continuous columns of segmental founder cells in the N lineage into distinct ganglionic primordia. We have examined the relationship between the N lineage cells that separate to form the fissures and lateral ectodermal and mesodermal derivatives by differentially labeling cells with intracellular lineage tracers and antibodies. Although subsets of both lateral ectoderm and muscle fibers contact N lineage cells at or near the time of fissure formation, ablation experiments suggest that these contacts are not required for initiating fissure formation. It appears, therefore, that this aspect of segmentation occurs autonomously within the N lineage. To support this idea, we present evidence that fundamental differences exist between alternating ganglionic precursor cells (nf and ns primary blast cells) within the N lineage. Specifically, ablation of an nf primary blast cell sometimes resulted in the fusion of ipsilateral hemi-ganglia, while ablation of an ns primary blast cell often caused a ‘slippage’ of blast cells posterior to the lesion. Also, differences in cell behavior were observed in biochemically arrested nf and ns primary blast cells. Collectively, these results lead to a model of segmentation in the leech CNS that is based upon differences in cell adhesion and/or cell motility between the alternating nf and ns primary blast cells. We note that the segmentation processes described here occur well prior to the expression of the leech engrailed-class gene in the N lineage.

Positional signaling by hedgehog in Drosophila imaginal disc development

Development ◽  
1995 ◽  
Vol 121 (1) ◽  
pp. 1-10 ◽  
Author(s):  
A.L. Felsenfeld ◽  
J.A. Kennison
Keyword(s):  
Hedgehog Signaling ◽  
Imaginal Disc ◽  
Ectopic Expression ◽  
Posterior Compartment ◽  
Anterior Compartment ◽  
Segment Polarity ◽  
Wing Structures ◽  
Wing Discs ◽  
Segment Polarity Gene ◽  
Polarity Gene

We describe a dominant gain-of-function allele of the segment polarity gene hedgehog. This mutation causes ectopic expression of hedgehog mRNA in the anterior compartment of wing discs, leading to overgrowth of tissue in the anterior of the wing and partial duplication of distal wing structures. The posterior compartment of the wing is unaffected. Other imaginal derivatives are affected, resulting in duplications of legs and antennae and malformations of eyes. In mutant imaginal wing discs, expression of the decapentaplegic gene, which is implicated in the hedgehog signaling pathway, is also perturbed. The results suggest that hedgehog protein acts in the wing as a signal to instruct neighboring cells to adopt fates appropriate to the region of the wing just anterior to the compartmental boundary.

rasp, a putative transmembrane acyltransferase, is required for Hedgehog signaling

Development ◽  
2002 ◽  
Vol 129 (4) ◽  
pp. 843-851 ◽  
Author(s):  
Craig A. Micchelli ◽  
Inge The ◽  
Erica Selva ◽  
Vladic Mogila ◽  
Norbert Perrimon
Keyword(s):  
Hedgehog Signaling ◽  
Transmembrane Protein ◽  
Post Translational Modification ◽  
Protein Levels ◽  
Lethal Mutations ◽  
Segment Polarity ◽  
Invertebrate Development ◽  
Membrane Bound ◽  
Segment Polarity Gene ◽  
Polarity Gene

Members of the Hedgehog (Hh) family encode secreted molecules that act as potent organizers during vertebrate and invertebrate development. Post-translational modification regulates both the range and efficacy of Hh protein. One such modification is the acylation of the N-terminal cysteine of Hh. In a screen for zygotic lethal mutations associated with maternal effects, we have identified rasp, a novel Drosophila segment polarity gene. Analysis of the rasp mutant phenotype, in both the embryo and wing imaginal disc demonstrates that rasp does not disrupt Wnt/Wingless signaling but is specifically required for Hh signaling. The requirement of rasp is restricted only to those cells that produce Hh; hh transcription, protein levels and distribution are not affected by the loss of rasp. Molecular analysis reveals that rasp encodes a multipass transmembrane protein that has homology to a family of membrane bound O-acyl transferases. Our results suggest that Rasp-dependent acylation is necessary to generate a fully active Hh protein.

Transcription of the segment-polarity gene wingless in the imaginal discs of Drosophila, and the phenotype of a pupal-lethal wg mutation

Development ◽  
1988 ◽  
Vol 102 (3) ◽  
pp. 489-497 ◽  
Author(s):  
N.E. Baker
Keyword(s):  
In Situ Hybridization ◽  
Imaginal Discs ◽  
Apical Cytoplasm ◽  
Segment Polarity ◽  
Disc Cells ◽  
Segment Polarity Gene ◽  
Drosophila Embryos ◽  
Polarity Gene

Wingless (wg) is a segment-polarity gene in Drosophila which is related to the murine proto-oncogene int1. In Drosophila embryos, wg transcription defines part of each parasegment. In situ hybridization shows that wg is also expressed in the imaginal discs which give rise to the adult during metamorphosis. Transcripts are localized in the apical cytoplasm of disc cells, and accumulate in different patterns in dorsal and ventral discs. The wgCX3 mutation produces morphological defect in the adult structures derived from these imaginal discs. The results show that wg is involved in the development of the adult, as well as the embryo, but that the imaginal discs do not express this segment-polarity gene in an identical pattern to the embryonic segments.

Ectopic expression of either the Drosophila gooseberry-distal or proximal gene causes alterations of cell fate in the epidermis and central nervous system

Development ◽  
1994 ◽  
Vol 120 (5) ◽  
pp. 1151-1161 ◽  
Author(s):  
Y. Zhang ◽  
A. Ungar ◽  
C. Fresquez ◽  
R. Holmgren
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Cell Fate ◽  
Ectopic Expression ◽  
Cell Fate Specification ◽  
Single Function ◽  
Independent Functions ◽  
Segment Polarity ◽  
The Central Nervous System ◽  
The Common

Previous studies have shown that the segment polarity locus gooseberry, which contains two closely related transcripts gooseberry-proximal and gooseberry-distal, is required for proper development in both the epidermis and the central nervous system of Drosophila. In this study, the roles of the gooseberry proteins in the process of cell fate specification have been examined by generating two fly lines in which either gooseberry-distal or gooseberry-proximal expression is under the control of an hsp70 promoter. We have found that ectopic expression of either gooseberry protein causes cell fate transformations that are reciprocal to those of a gooseberry deletion mutant. Our results suggest that the gooseberry-distal protein is required for the specification of naked cuticle in the epidermis and specific neuroblasts in the central nervous system. These roles may reflect independent functions in neuroblasts and epidermal cells or a single function in the common ectodermal precursor cells. The gooseberry-proximal protein is also found in the same neuroblasts as gooseberry-distal and in the descendants of these cells.

The segment polarity gene armadillo interacts with the wingless signaling pathway in both embryonic and adult pattern formation

Development ◽  
1991 ◽  
Vol 111 (4) ◽  
pp. 1029-1043 ◽  
Author(s):  
M. Peifer ◽  
C. Rauskolb ◽  
M. Williams ◽  
B. Riggleman ◽  
E. Wieschaus
Keyword(s):  
Pattern Formation ◽  
Imaginal Discs ◽  
Protein Accumulation ◽  
Segment Polarity Genes ◽  
Adult Pattern ◽  
Segment Polarity ◽  
Lethal Allele ◽  
Segment Polarity Gene ◽  
Polarity Gene

The segment polarity genes of Drosophila were initially defined as genes required for pattern formation within each embryonic segment. Some of these genes also function to establish the pattern of the adult cuticle. We have examined the role of the armadillo (arm) gene in this latter process. We confirmed and extended earlier findings that arm and the segment polarity gene wingless are very similar in their effects on embryonic development. We next discuss the role of arm in pattern formation in the imaginal discs, as determined by using a pupal lethal allele, by analyzing clones of arm mutant tissue in imaginal discs, and by using a transposon carrying arm to produce adults with a reduced level of arm. Together, these experiments established that arm is required for the development of all imaginal discs. The requirement for arm varies along the dorsal-ventral and proximal-distal axes. Cells that require the highest levels of arm are those that express the wingless gene. Further, animals with reduced arm levels have phenotypes that resemble those of weak alleles of wingless. We present a description of the patterns of arm protein accumulation in imaginal discs. Finally, we discuss the implications of these results for the role of arm and wingless in pattern formation.

Ablation of Tumor-Derived Stem Cells Transplanted to the Central Nervous System by Genetic Modification of Embryonic Stem Cells with a Suicide Gene

2007 ◽  
Vol 18 (12) ◽  
pp. 1182-1192 ◽  
Author(s):  
Juyeon Jung ◽  
Neil R. Hackett ◽  
Robert G. Pergolizzi ◽  
Lorraine Pierre-Destine ◽  
Anja Krause ◽  
...  
Keyword(s):  
Stem Cells ◽  
Central Nervous System ◽  
Nervous System ◽  
Embryonic Stem Cells ◽  
Genetic Modification ◽  
Embryonic Stem ◽  
Suicide Gene ◽  
The Central Nervous System

Arsenic Trioxide Entered Cerebrospinal Fluid with the Help of Mannitol Overwhelm the Meningeal Relapse of Acute Promyelocytic Leukemia.

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 946-946
Author(s):  
Jin Zhou ◽  
Ran Meng ◽  
Xinhua Sui ◽  
Guosheng Feng ◽  
Baoyu Li
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Arsenic Trioxide ◽  
Intravenous Infusion ◽  
Intrathecal Chemotherapy ◽  
10Mg Dose ◽  
Arsenic Level ◽  
Cns Relapse ◽  
Blast Cells ◽  
Elemental Arsenic

Abstract Background and objective Central nervous system (CNS) relapse of acute promyeloytic leukemia (APL) is increasingly reported after treatment with all-trans retinoic acid (ATRA) and arsenic trioxide (As2O3), the optimal therapy for these cases remains unclear. As2O3 highly effective in APL marrow relapse, but its efficacy in APL CNS relapse is undefined. Recent researches showed that little As2O3 could pass through the intact blood- brain-barrier (BBB), which limits its use in prevention and treatment of central nervous system acute promyelocytic leukaemia (CNSAPL). After discovered the different tolarance between NB4 cell line and human cortex neuron to As2O3in vitro, and primarily cleared the safe range of As2O3 level in central nervous system (CNS), we created a non-invasive method to help As2O3 enter into CNS effectively. Methods Five volunteers with isolated meningle APL relapse received the new As2O3 regimen (mannitol helped As2O3 penetration) after accepted the conventional treatment: As2O3 0.16mg/kg/d diluted with 5%glucose 250ml common speed intravenous infusion with intensive intrathecal chemotherapy (MTX 12mg/dose + cytarabine 50mg / dose + Dexamethasone 10mg/dose) and showed chemotherapy resistance. The new regimen included 125ml of 20% mannitol bolus through medial cubital vein with the speed of 12„d`30ml / min, followed by As2O3 0.08mg/kg/d diluted with 250ml-20% mannitol intravenous infusion with the speed of 6ml /min, and then followed by As2O3 0.08mg/kg/d diluted with 5%glucose 250ml intravenous infusion with the speed of 0.5ml/min, meanwhile, associated with intensive intrathecal chemotherapy. The elemental arsenic levels in CSF and plasma during the new regimen performance were dynamic monitored with atomic fluorescence, and the differentiation and apoptosis of the blast cells in CSF were detected with flow cytometry assay. Results The elemental arsenic level in the CSF treated with mannitol helped As2O3 penetration was fluctuated between 0.04 mg /L (0.2 micromol /L) and 0.05mg / L(0.25 micromol /L), which was much higher than that with common speed As2O3 intravenous infusion, and reached to the As2O3 effectively therapeutic level. The blast cells in CSF showed significant differentiation and apoptosis after treated with mannitol helped As2O3 penetration. Three of the five patients obtained complete remission, two of them reached partial remission. Conclusions The new regimen of mannitol helped As2O3 penetration promoted the entrance of elemental arsenic to CNS, which might be benefit to prevent and cure CNS APL, especially to chemotherapy resistant CNS APL.

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