Developmental origin of segmental identity in the leech mesoderm

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.


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 (3) ◽  
pp. 857-871 ◽  
Author(s):  
D. Lans ◽  
C.J. Wedeen ◽  
D.A. Weisblat

ht-en is an engrailed-class gene that is expressed during early development and neurogenesis in embryos of the leech Helobdella triserialis. During the early development of this annelid (stages 7–9), ht-en is expressed in each of the ectodermal and mesodermal teloblast lineages that contributes progeny to the definitive segments. ht-en is expressed transiently by individually identified cells within the segmentally iterated primary blast cell clones. Its expression is correlated with the age of the primary blast cell clone. After consegmental primary blast cell clones from the different teloblast lineages have come into segmental register, cells that express ht-en during stages 7–9 are clearly confined to a transverse region corresponding to the posterior portion of the segmental anlage, but not all cells within this region express ht-en. Only a minority of the identified cells that express ht-en during terminal differentiation of the segmental ganglia and body wall (stages 10–11) are descendants of cells that express ht-en in early development (stages 7–9).


Development ◽  
1989 ◽  
Vol 107 (4) ◽  
pp. 855-862 ◽  
Author(s):  
S. Tix ◽  
M. Bate ◽  
G.M. Technau

Injection of a cell lineage tracer (HRP) into Drosophila embryos before cellularization provides a way of selectively labelling cells at later stages that have undergone only a few mitoses. All cells born and differentiating during embryogenesis become labelled, whereas further proliferation and growth during postembryonic development causes an almost complete dilution of the marker in the adult cell complement. Early born neurons visualized in this way are good candidates for executing a pioneering function during postembryonic differentiation of the adult nervous system. In all three pairs of leg imaginal discs, a stereotyped set of larval sense organs becomes selectively labelled. Their axons fasciculate with a larval nerve, which connects the leg disc with the central nervous system. Larval sense organs are not present in the other imaginal discs. Larval neurons are not present in the transformed antennal discs of Antp 73B flies. Nonetheless adult axons successfully navigate to the base of these discs as they differentiate to form ectopic legs. We conclude that embryonically formed larval nerves are not essential for the guidance of adult axons within the leg discs.


2020 ◽  
Author(s):  
Irepan Salvador-Martínez ◽  
Marco Grillo ◽  
Michalis Averof ◽  
Maximilian J Telford

Recent innovations in genetics and imaging are providing the means to reconstruct cell lineages, either by tracking cell divisions using live microscopy, or by deducing the history of cells using molecular recorders. A cell lineage on its own, however, is simply a description of cell divisions as branching events. A major goal of current research is to integrate this description of cell relationships with information about the spatial distribution and identities of the cells those divisions produce. Visualising, interpreting and exploring these complex data in an intuitive manner requires the development of new tools. Here we present CeLaVi, a web-based visualisation tool that allows users to navigate and interact with a representation of cell lineages, whilst simultaneously visualising the spatial distribution, identities and properties of cells. CeLaVi's principal functions include the ability to explore and manipulate the cell lineage tree; to visualise the spatial distribution of cell clones at different depths of the tree; to colour cells in the 3D viewer based on lineage relationships; to visualise various cell qualities on the 3D viewer (e.g. gene expression, cell type, tissue layer) and to annotate selected cells/clones. All these capabilities are demonstrated with four different example data sets. CeLaVi is available at http://www.celavi.pro.


Blood ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. 2562-2562
Author(s):  
Jian Chen ◽  
Agnieszka Wendorff ◽  
Yue Li ◽  
Johann K. Hitzler

Abstract Abstract 2562 Background. Transient leukemia (TL), a disorder of fetal hematopoiesis, occurs in approximately 10% of infants with Down syndrome and in one fifth of cases is followed by the development of acute myeloid leukemia. The diagnosis of TL is based on the detection of a spontaneously resolving population of blasts in the peripheral blood of newborns with DS and, more recently, the detection of clone-specific somatic mutations of the hematopoietic transcription factor GATA1. The alternative terms for this condition, transient myeloproliferative disorder (TMD) and transient abnormal myelopoiesis (TAM), reflect the observation that the peripheral blood of affected infants frequently shows an expansion of immature granulocytic precursor cells at various stages of development as well as nucleated erythroid precursors in addition to a population of blast cells. We hypothesized that the immature myeloid precursor cells observed in TL arise from the same hematopoietic cell clone that is defined by the specific GATA1 mutation found in TL blasts. Methods. Cryopreserved mononuclear cells from peripheral blood samples of three male infants with TL of Down syndrome were stained at a density of 106 cells/100ul with the following antibodies: CD45-Alexa Flour 700, CD61-PE, CD11b-PE-Cy5, CD235a-PE-Cy7, CD3-APC, CD34-APC-Cy7, CD15-Pacific Blue. In addition, aliquots of these cell populations were fixed, permeabilized and stained with for intracellular myeloperoxidase (MPO-FITC). Fractions of cells corresponding to different hematopoietic lineages were prepared by fluorescence activated cell sorting (FACSAriaII, BD Biosciences, San Jose, CA) both as bulk populations and single cells (sorted into 96-well plates). Morphology of sorted cell populations was determined by Giemsa staining. Lineage-specific hematopoietic colonies were cultured from primary mononuclear cell samples in a standard CFC assay. DNA of sorted bulk and single cell populations as well as individual lineage-specific hematopoietic colonies was used to detect GATA1 mutations in exon 2 by PCR, restriction enzyme analysis or sequencing of PCR products, or nested PCR. The location of the GATA1 gene on the X chromosome and the use of samples derived from males meant that wild type GATA1 alleles were not derived from TL cells. Results. Primary TL blood samples could be fractionated in a blast cell (CD45+CD34+and/or CD61+), erythroid (CD45-CD235a+), immature myeloid (CD45+CD15+MPO+) and lymphoid (CD45+CD3+) cell population. Cell morphology was consistent with this sorting strategy. The cell fraction designed to enrich TL blasts in all cases showed the presence of cells harboring only the mutant GATA1 allele indicating a high degree of purity of the blast fraction. As expected, the lymphoid cell populations contained in the CD3+ fractions exclusively harbored wild type alleles. Similarly, both sorted erythroid cell populations and individual erythroid colonies (Bfu-E) derived from unsorted input cells harbored only wild type GATA1 alleles. In contrast, CD15+ and/or MPO+ myeloid cell fractions consistently showed the presence of both mutant and wild type GATA1 alleles. Quantification by single cell PCR is in progress. Conclusion. Somatic GATA1 mutations which result in the translation of a N-terminally truncated mutant protein (GATA1s), are pathognomonic for TL and myeloid leukemia of Down syndrome. Published data do not determine if the cell clone harboring GATA1 mutations in TL extends beyond the population of blast cells and megakaryocytic lineage. We confirmed the presence of GATA1 mutations in TL blasts and their expected absence from lymphoid cell populations. The absence of mutations from cells of erythroid lineage suggests that the altered GATA1 function induced by mutations found in TL is incompatible with erythroid differentiation. The detection of clone-specific GATA1 mutations in myeloid cells expressing MPO was unexpected and raises the possibility that either the progenitor cells giving rise to TL blasts or the blasts themselves retain myeloid lineage differentiation potential. The finding lends support to definitions of TL and myeloid leukemia in Down syndrome that are based on the specific mutational and cellular mechanism and transcend a megakaryoblastic blast phenotype. Disclosures: No relevant conflicts of interest to declare.


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.


1998 ◽  
Vol 353 (1370) ◽  
pp. 925-933 ◽  
Author(s):  
Nicholas A. Wright

The main pathways of epithelial differentiation in the intestine, Paneth, mucous, endocrine and columnar cell lineages are well recognized. However, in abnormal circumstances, for example in mucosal ulceration, a cell lineage with features distinct from these emerges, which has often been dismissed in the past as ‘pyloric’ metaplasia, because of its morphological resemblance to the pyloric mucosa in the stomach. However, we can conclude that this cell lineage has a defined phenotype unique in gastrointestinal epithelia, has a histogenesis that resembles that of Brunner's glands, but acquires a proliferative organization similar to that of the gastric gland. It expresses several peptides of particular interest, including epidermal growth factor, the trefoil peptides TFF1, TFF2, TFF3, lysozyme and PSTI. The presence of this lineage also appears to cause altered gene expression in adjacent indigenous cell lineages. We propose that this cell lineage is induced in gastrointestinal stem cells as a result of chronic mucosal ulceration, and plays an important part in ulcer healing; it should therefore be added to the repertoire of gastrointestinal stem cells.


Blood ◽  
2012 ◽  
Vol 119 (19) ◽  
pp. 4349-4357 ◽  
Author(s):  
Fanny Guimont-Desrochers ◽  
Geneviève Boucher ◽  
Zhongjun Dong ◽  
Martine Dupuis ◽  
André Veillette ◽  
...  

Abstract The cell lineage origin of IFN-producing killer dendritic cells (IKDCs), which exhibit prominent antitumoral activity, has been subject to debate. Although IKDCs were first described as a cell type exhibiting both plasmacytoid DC and natural killer (NK) cell properties, the current view reflects that IKDCs merely represent activated NK cells expressing B220, which were thus renamed B220+ NK cells. Herein, we further investigate the lineage relation of B220+ NK cells with regard to other NK-cell subsets. We surprisingly find that, after adoptive transfer, B220− NK cells did not acquire B220 expression, even in the presence of potent activating stimuli. These findings strongly argue against the concept that B220+ NK cells are activated NK cells. Moreover, we unequivocally show that B220+ NK cells are highly proliferative and differentiate into mature NK cells after in vivo adoptive transfer. Additional phenotypic, functional, and transcriptional characterizations further define B220+ NK cells as immediate precursors to mature NK cells. The characterization of these novel attributes to B220+ NK cells will guide the identification of their ortholog in humans, contributing to the design of potent cancer immunotherapies.


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