Origin of segmental identity in the development of the leech nervous system

Development ◽  
1991 ◽  
Vol 113 (Supplement_2) ◽  
pp. 29-38 ◽  
Author(s):  
Marty Shankland ◽  
Mark Q. Martindale ◽  
Denise Nardelli-Haefliger ◽  
Euan Baxter ◽  
David J. Price

The leech embryo develops its segmental body plan by means of a stereotyped cell lineage. Each hemilateral segment arises from a small set of embryonic blast cells via a comparable sequence of formative cell divisions, and for the most part, lineally homologous cells manifest similar patterns of differentiation in the various heniisegments. Nonetheless, some identified central neurons undergo segment-specific or laterally asymmetric patterns of neuropeptide expression and/or cell death. Certain aspects of this regional diversification result from competitive cell interactions which occur at the level of the postmitotic neuron. However, the neuron's segmental identity is lineally determined, being inherited from its blast cell progenitor over several intervening rounds of mitosis. To learn more about the molecular basis of this phenomenon, we have isolated and begun to characterize leech homeobox genes which are related to the genes that govern segmental identity in other organisms.

Development ◽  
1993 ◽  
Vol 117 (1) ◽  
pp. 177-189 ◽  
Author(s):  
L. Gleizer ◽  
G.S. Stent

Segmentation in the leech embryo is established by a stereotyped cell lineage. Each of the 32 segments arises from homologous, bilaterally symmetrical complements of mesodermal and ectodermal blast cell clones. Although segments are homologous, they are regionally differentiated along the longitudinal body axis. Various segments display idiosyncratic ensembles of features, which constitute discrete segmental identities. The differentiation of segment-specific features, such as the mesoderm-derived nephridia, genital primordia and identified Small Cardioactive Peptide immunoreactive neurons, reflects a diversification of the developmental fates of homologous blast cell clones. We have investigated whether segment-specific differentiation of homologous mesodermal blast cell clones depends on cell-intrinsic mechanisms (based on the cells' lineage history) or on cell-extrinsic mechanisms (based on the cells' interactions with their environment) in embryos of Theromyzon rude. For this purpose, we first mapped the segment-specific fates of individual mesodermal blast cell clones, and then induced mesodermal clones to take part in the formation of segments for which they are not normally destined. Two types of ectopic segmental position were produced: one in which a mesodermal blast cell clone was out of register with all other consegmental cells and one in which a mesodermal blast cell clone was out of register with its overlying ectoderm, but was in normal register with the mesoderm and ectoderm on the other side of the embryo. Mesodermal blast cell clones that developed in either type of ectopic segmental position gave rise to segment-specific features characteristic of their original segmental fates rather than their ectopic positions. Thus, the development of segmental identity in the leech mesoderm is attributable to a cell-intrinsic mechanism and, either before or soon after their birth, mesodermal blast cells are autonomously committed to segment-specific fates.


Segments in the leech arise by the proliferation of longitudinally arrayed bandlets of blast cells derived from ten identifiable embryonic stem cells, two M, two N, four O /P and two Q teloblasts. In each bandlet, older blast cells lie ahead of those born later. By using microinjected cell lineage tracers it was shown previously that the teloblasts give rise to characteristic cell patterns made up of segmentally iterated complements of progeny designated as M, N, O, P and Q kinship groups. When a teloblast is injected after it has begun generating blast cells, a boundary is observed later in development between anterior, unlabelled progeny of blast cells produced before injection and posterior, labelled progeny of blast cells produced after injection. We have examined such boundaries in detail to establish the precise relationship between blast cell clones and segments, with the following conclusions: (i) in the M, O and P cell lines, one blast cell generates one segmental complement of progeny, but serially homologous blast clones intermix so that no segment boundaries can be defined based on primary blast cell clones; (ii) in the N and Q cell lines, two blast cells are required to generate a complete segmental complement of progeny; (iii) in the process of forming the germinal plate, cells derived from the N and Q teloblasts move past those derived from the M and O /P teloblasts, so that consegmental blast cell clones do not come into register until well after the establishment of segmentally iterated units within each bandlet.


1984 ◽  
Vol 52 (03) ◽  
pp. 301-304 ◽  
Author(s):  
L Gugliotta ◽  
Silvana Viganò ◽  
A D’Angelo ◽  
Anna Guarini ◽  
S Tura ◽  
...  

SummaryPlasma levels of fibrinopeptide A (FPA) in 30 untreated patients with acute non-lymphocytic leukemia (ANLL) were significantly higher than in 30 healthy controls (p <0.001). Patients without laboratory signs of disseminated intravascular coagulation (DIC) had levels of FPA higher than controls (p <0.02) but markedly lower than patients with DIC (p <0.001). Five patients with M3 leukemia had a higher mean FPA level (p <0.02) and a lower peripheral blast cell count (p <0.05) than patients with other cytological subtypes of ANLL. When patients with M3 were excluded, a significant correlation was observed between the peripheral blast cell counts and the FPA levels (r = 0.66, p <0.001). FPA levels were similar with body temperature either above or below 38° C. After intravenous bolus of heparin FPA dropped to normal levels in 14 out of 17 patients who had high baseline values. These findings indicate that intravascular thrombin formation, which probably result from the expression of procoagulant activities of blast cells, is the main cause of high FPA in the majority of patients with acute non-lymphocytic leukemia.


Genetics ◽  
1980 ◽  
Vol 96 (2) ◽  
pp. 435-454 ◽  
Author(s):  
H Robert Horvitz ◽  
John E Sulston

ABSTRACT Twenty-four mutants that alter the normally invariant post-embryonic cell lineages of the nematode Caenorhabditis elegans have been isolated and genetically characterized. In some of these mutants, cell divisions fail that occur in wild-type animals; in other mutants, cells divide that do not normally do so. The mutants differ in the specificities of their defects, so that it is possible to identify mutations that affect some cell lineages but not others. These mutants define 14 complementation groups, which have been mapped. The abnormal phenotype of most of the cell-lineage mutants results from a single recessive mutation; however, the excessive cell divisions characteristic of one strain, CB1322, require the presence of two unlinked recessive mutations. All 24 cell-lineage mutants display incomplete penetrance and/or variable expressivity. Three of the mutants are suppressed by pleiotropic suppressors believed to be specific for null alleles, suggesting that their phenotypes result from the complete absence of gene activity.


Blood ◽  
1978 ◽  
Vol 52 (3) ◽  
pp. 592-600 ◽  
Author(s):  
MD Minden ◽  
JE Till ◽  
EA McCulloch

Abstract Peripheral blood from patients with acute myeloblastic leukemia (AML) contains cells capable of giving rise to colonies in culture when stimulated by media conditioned by leukocytes (LCM) in the presence of phytohemagglutinin (PHA). Two types of colonies are recognized with high frequency: The first grows in the presence of low concentrations of PHA LCM, have a blast-like morphology, and are numerically correlated with morphologically identified blast cells. The second requires either high PHA LCM concentrations or PHA alone with or without 2-mercaptoethanol and consists of cells capable of forming rossettes with sheep erythrocytes and resembles. T-lymphocyte colonies from normal blood. Precursors of blast cell colonies from 15 leukemic patients were tested for cycle state, using either the 3H-thymidine or hydroxyurea techniques. All were found to have a high proportion of cells in the S phase of the cycle. In contrast, T lymphocyte precursors from three normal individual were quiescent. The data are consistent with the maintenance of the leukemic blast cell populations by the proliferative activity of a small subpopulation of blasts.


Blood ◽  
2000 ◽  
Vol 96 (7) ◽  
pp. 2543-2549 ◽  
Author(s):  
Nancy R. Schneider ◽  
Andrew J. Carroll ◽  
Jonathan J. Shuster ◽  
D. Jeanette Pullen ◽  
Michael P. Link ◽  
...  

Abstract To further define the cytogenetic differences between B-cell lineage (B-lineage) acute lymphoblastic leukemia (ALL) and T-cell lineage ALL (T-ALL) and to determine the prognostic value of cytogenetics in childhood T-ALL, the blast cell karyotypes of 343 cases of pediatric T-ALL, the largest series reported to date, were evaluated. Cytogenetics were performed in a single central laboratory, and the children were treated using a single Pediatric Oncology Group protocol. Clear differences between the karyotypic characteristics of B-lineage ALL and T-ALL were confirmed. This study suggests that there may be survival differences associated with some T-ALL blast cell karyotypes. Better survival is associated with only normal karyotypes and with t(10;14) (translocation of chromosomes 10 and 14); worse survival is associated with the presence of any derivative chromosome. Two new recurring chromosome aberrations previously not reported in T-ALL were found: del(1)(p22) and t(8;12)(q13;p13). Ten aberrations found in this series, which were reported only once previously in T-ALL, can now be considered recurring abnormalities in T-ALL. All 12 of these new recurring aberrations are targets for discovery and characterization of new genes that are important in T-cell development and leukemogenesis.


Blood ◽  
1982 ◽  
Vol 59 (6) ◽  
pp. 1203-1206 ◽  
Author(s):  
R Billing ◽  
K Lucero ◽  
BJ Shi ◽  
PI Terasaki

Abstract A monoclonal mouse antibody has been raised to the common acute lymphoblastic leukemia (cALL) cell line Reh. It is a cytotoxic antibody of the IgG2, subclass that reacts with leukemia cells from the following patients: 69% non-B non-T ALL, 50% T-ALL, 18% acute myeloblastic leukemia (AML), and 66% chronic myeloid leukemia (CML) blast crisis lymphoid cells. Other types of leukemia and all normal blood cells tested were negative, including T and B lymphocytes, granulocytes, monocytes, erythrocytes, and spleen cells. The detected antigen appears to be a type of blast cell antigen because it is also present on phytohemagglutinin (PHA) blast cells, myeloblast from normal bone marrow cells (by CFU-C), and all lymphoblastoid cell lines tested. Only one active antibody species could be detected by preparative isoelectric focusing on polyacrylamide gels and by protein-A-Sepharose affinity chromatography.


1978 ◽  
Vol 147 (3) ◽  
pp. 912-922 ◽  
Author(s):  
S K Lee ◽  
R T Oliver

Short-term culture of acute myelogenous leukemia patient's remission lymphocytes with inactivated autologous leukemic blast cells plus allogeneic lymphocytes, generated effector T lymphocytes which were cytotoxic for the specific autologous blast cell in 11 of 14 patients studied. Experiments using Daudi and Molt 4 lymphoblastoid cell lines as third-party helper cell suggest that an HLA D locus incompatability is necessary to provide effective help in this system. Cold target inhibition experiments, crossover studies between pairs of patients, and experiments with allogeneic leukemic blast cells as priming stimulus suggest that the target antigen is only present on the specific autologous blast cell.


Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 4472-4472
Author(s):  
Maria-Belen Vidriales ◽  
Lilia Suarez ◽  
José García-Laraña ◽  
Antonio López ◽  
María José Moreno ◽  
...  

Abstract Elderly AML patients have an unfavorable prognosis with frequent resistance of leukemic cells to chemotherapy. The expression of proteins related with apoptosis and multi-drug resistance have been involved in chemotherapeutic resistance in AML; however, these proteins are not only expressed on leukemic but also on normal cells. Moreover, within leukemic cells, different stages of maturation may occur. The aim of the present study was to evaluate the expression of proteins related to apoptosis (APO 2.7, bax, and bcl-2), and drug resistance (P-gp, MRP, LRP) in a series of 117 elderly AML patients (median age of 70) uniformly treated according with the Spanish Pethema cooperative group protocol (LMA &gt;65). 63 patients (54%) achieved complete remission (CR), with a median relapse free survival (RFS) of 9.2 months. In the bone marrow (BM) pre-treatment, we performed a four-color staining technique (APO2.7, bax or bcl-2 with CD32/CD34/CD45; and P-gp, MRP, or LRP with CD34/CD19/CD33), allowing the identification of myeloid blast cells, and the discrimination between stages of maturation of blast cell subsets. Samples were acquired on a FACSCalibur flow cytometer (Becton/Dickinson), and appropriate controls were used in each individual sample and, accordingly, antigen expression in individual cell samples was quantified as relative fluorescence intensity (RFI) (ratio blast cell/control mean channel fluorescence value). Our results showed that the level of expression of MRP and LRP was significantly higher (mean±SD of MFI 2.0±0.75 vs 2.7±1.87 and 4.5±2.2 vs 7.0±6.2, respectively -p &lt;0.03-) in cases that did not achieved CR with one or two cycles of chemotherapy. Although different patterns of expression of apoptosis or drug resistance-associated proteins were detected according with the stage of maturation on myeloid blast cells, we did’t found any other correlation between levels of bcl-2, bax, APO 2.7, bcl-2/bax ratio or MDR and probability of achieving morphological CR. In addition, CD34 expression on blast cells had also significant influence on response (CR was achieved in 81% of CD34 negative cases vs only 46% of CD34 positive cases; p= 0.005). We didn’t found any influence of apoptosis and/or drug-resistance proteins expression in relapse rate nor RFS. Variables influencing RFS were age (p=0.04), and number of cycles to achieve CR (p=0.01); while only WBC count (p=0.05) influenced overall survival (OS). We conclude that MRP and LRP could have a role in the resistance to induction treatment in elderly AML patients but not in RFS or OS.


Development ◽  
1997 ◽  
Vol 124 (12) ◽  
pp. 2441-2450 ◽  
Author(s):  
C.B. Reid ◽  
S.F. Tavazoie ◽  
C.A. Walsh

Cell lineage analysis with retroviral libraries suggests that clonal progeny disperse widely in rodent cortex. To determine whether widespread dispersion is a general mammalian plan and to investigate phylogenetic differences in cortical development, we analyzed cell lineage in the ferret, a carnivore and near relative of the cat. The ferret possesses a highly developed, folded cerebral cortex, characteristic of higher mammalian species. Progenitor cells of the ferret cerebral cortex were tagged with an amphotropic retroviral library encoding alkaline phosphatase, and sibling relationships were determined using the polymerase chain reaction. Neuronal clones were single neurons (52%) or large clones (48%; average, 7 neurons) containing neurons and glia in widespread cortical locations. Neuronal clones in the ferret labeled at middle to late neurogenesis (embryonic day 33–35) contained large numbers of neurons and showed little tendency to cluster. The large proportion of single neuron clones, contrasted with the large size of multicell clones, suggests that some progenitors divide asymmetrically, producing a postmitotic neuron and regenerating a multipotential cell.


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