Micromere fate maps in leech embryos: lineage-specific differences in rates of cell proliferation

Stereotyped early cleavages in glossiphoniid leech embryos yield 25 micromeres, along with 3 macromeres and 10 teloblasts. The micromeres generate prostomial tissues and also give rise to most of the squamous epithelium of a provisional integument that spreads epibolically from the animal pole, covering the rest of the embryo during germinal plate formation. We systematically injected individual micromeres with fluorescent cell lineage tracers at the time of their birth and quantitatively mapped the contributions of all these cells to the late stage 7 embryo, a time in development that is early in the epibolic expansion. At this time, micromere derivatives comprise two types of cells: squamous epithelial (superficial) cells that cover the germinal bands and the region of the animal cap between the germinal bands; and underlying (deep) cells that are confined to the distal ends of the germinal bands and in the area between their distal ends. We find that individual micromeres contribute clones of deep and/or superficial progeny that are stereotyped with respect to both numbers and types of cells in the clone and the domains that they occupy. The N teloblasts also contribute cells to the squamous epithelium. We find significant differences in the rate of cell proliferation between different micromere clones. These differences appear to reflect lineage-specific traits, since there is little or no regulation of cell number after ablation of individual micromeres.

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Cell fate clusters in ICM organoids arise from cell fate heredity and division: a modelling approach

Scientific Reports ◽

10.1038/s41598-020-80141-3 ◽

2020 ◽

Vol 10 (1) ◽

Author(s):

Tim Liebisch ◽

Armin Drusko ◽

Biena Mathew ◽

Ernst H. K. Stelzer ◽

Sabine C. Fischer ◽

...

Keyword(s):

Cell Proliferation ◽

Cell Division ◽

Cell Fate ◽

Inner Cell Mass ◽

Cell Mass ◽

Cell Lineage ◽

Cell Fate Decision ◽

Cell Fate Decisions ◽

Chemical Signalling ◽

Fate Decision

AbstractDuring the mammalian preimplantation phase, cells undergo two subsequent cell fate decisions. During the first decision, the trophectoderm and the inner cell mass are formed. Subsequently, the inner cell mass segregates into the epiblast and the primitive endoderm. Inner cell mass organoids represent an experimental model system, mimicking the second cell fate decision. It has been shown that cells of the same fate tend to cluster stronger than expected for random cell fate decisions. Three major processes are hypothesised to contribute to the cell fate arrangements: (1) chemical signalling; (2) cell sorting; and (3) cell proliferation. In order to quantify the influence of cell proliferation on the observed cell lineage type clustering, we developed an agent-based model accounting for mechanical cell–cell interaction, i.e. adhesion and repulsion, cell division, stochastic cell fate decision and cell fate heredity. The model supports the hypothesis that initial cell fate acquisition is a stochastically driven process, taking place in the early development of inner cell mass organoids. Further, we show that the observed neighbourhood structures can emerge solely due to cell fate heredity during cell division.

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Müllerian Inhibiting Substance Is Required for Germ Cell Proliferation during Early Gonadal Differentiation in Medaka (Oryzias latipes)

Endocrinology ◽

10.1210/en.2007-1535 ◽

2007 ◽

Vol 149 (4) ◽

pp. 1813-1819 ◽

Cited By ~ 47

Author(s):

Eri Shiraishi ◽

Norifumi Yoshinaga ◽

Takeshi Miura ◽

Hayato Yokoi ◽

Yuko Wakamatsu ◽

...

Keyword(s):

Cell Proliferation ◽

Germ Cell ◽

Germ Cells ◽

Sex Differentiation ◽

Somatic Cells ◽

Oryzias Latipes ◽

Cell Number ◽

Gonadal Differentiation ◽

Loss Of Function ◽

Germ Cell Proliferation

Müllerian inhibiting substance (MIS) is a glycoprotein belonging to the TGF-β superfamily. In mammals, MIS is responsible for the regression of Müllerian ducts in the male fetus. However, the role of MIS in gonadal sex differentiation of teleost fish, which have no Müllerian ducts, has yet to be clarified. In the present study, we examined the expression pattern of mis and mis type 2 receptor (misr2) mRNAs and the function of MIS signaling in early gonadal differentiation in medaka (teleost, Oryzias latipes). In situ hybridization showed that both mis and misr2 mRNAs were expressed in the somatic cells surrounding the germ cells of both sexes during early sex differentiation. Loss-of-function of either MIS or MIS type II receptor (MISRII) in medaka resulted in suppression of germ cell proliferation during sex differentiation. These results were supported by cell proliferation assay using 5-bromo-2′-deoxyuridine labeling analysis. Treatment of tissue fragments containing germ cells with recombinant eel MIS significantly induced germ cell proliferation in both sexes compared with the untreated control. On the other hand, culture of tissue fragments from the MIS- or MISRII-defective embryos inhibited proliferation of germ cells in both sexes. Moreover, treatment with recombinant eel MIS in the MIS-defective embryos dose-dependently increased germ cell number in both sexes, whereas in the MISRII-defective embryos, it did not permit proliferation of germ cells. These results suggest that in medaka, MIS indirectly stimulates germ cell proliferation through MISRII, expressed in the somatic cells immediately after they reach the gonadal primordium.

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STUDIES IN THE BIOLOGY OF METALS

Journal of Experimental Medicine ◽

10.1084/jem.48.5.659 ◽

1928 ◽

Vol 48 (5) ◽

pp. 659-665 ◽

Cited By ~ 15

Author(s):

Frederick S. Hammett ◽

Vilma L. Wallace

Keyword(s):

Cell Proliferation ◽

Chick Embryo ◽

Body Length ◽

Rapid Growth ◽

Cell Number ◽

Point Of View ◽

Lead Ion ◽

Head Region ◽

Differential Development

Our study of the effect of the lead ion on the development of the chick embryo has brought out the following facts: 1. Gross growth is retarded. 2. Somite growth is retarded to a degree greater than that exhibited by body length and width. 3. The head and optic anlagen are regions of particular sensitivity. Their differential development is markedly inhibited. From the purely biological point of view these results are in line with the findings of Child (10) and his school as to the sensitivity of the head end of rapidly growing organisms to harmful influences, and with those of Stockard (11) as to the peculiar sensitivity of the optic anlagen. It is almost too well known to need repetition that the head region and the somites of embryos are specific areas of intense growth by increase in cell number. Therefore, turning from the general to the particular, the differential retardation of these regions which is caused by lead, is evidence justifying the conclusion that it is areas of rapid growth by cell proliferation which are selectively inhibited by this metallic ion.

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Anteroposterior patterning in the zebrafish, Danio rerio: an explant assay reveals inductive and suppressive cell interactions

Development ◽

10.1242/dev.122.6.1873 ◽

1996 ◽

Vol 122 (6) ◽

pp. 1873-1883 ◽

Cited By ~ 8

Author(s):

C.G. Sagerstrom ◽

Y. Grinblat ◽

H. Sive

Keyword(s):

Danio Rerio ◽

Neural Induction ◽

Active Role ◽

Cell Number ◽

Type I ◽

Animal Pole ◽

Anteroposterior Patterning ◽

Embryonic Shield ◽

Low Levels ◽

Neural Markers

We report the first extended culture system for analysing zebrafish (Danio rerio) embryogenesis with which we demonstrate neural induction and anteroposterior patterning. Explants from the animal pole region of blastula embryos ('animal caps') survived for at least two days and increased in cell number. Mesodermal and neural-specific genes were not expressed in cultured animal caps, although low levels of the dorsoanterior marker otx2 were seen. In contrast, we observed strong expression of gta3, a ventral marker and cyt1, a novel type I cytokeratin expressed in the outer enveloping layer. Isolated ‘embryonic shield’, that corresponds to the amphibian organizer and amniote node, went on to express the mesodermal genes gsc and ntl, otx2, the anterior neural marker pax6, and posterior neural markers eng3 and krx20. The expression of these genes defined a precise anteroposterior axis in shield explants. When conjugated to animal caps, the shield frequently induced expression of anterior neural markers. More posterior markers were rarely induced, suggesting that anterior and posterior neural induction are separable events. Mesodermal genes were also seldom activated in animal caps by the shield, demonstrating that neural induction did not require co-induction of mesoderm in the caps. Strikingly, ventral marginal zone explants suppressed the low levels of otx2 in animal caps, indicating that ventral tissues may play an active role in axial patterning. These data suggest that anteroposterior patterning in the zebrafish is a multi-step process.

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The Polycomb group protein MEDEA controls cell proliferation and embryonic patterning in Arabidopsis

10.1101/2020.10.13.338707 ◽

2020 ◽

Author(s):

Sara Simonini ◽

Marian Bemer ◽

Stefano Bencivenga ◽

Valeria Gagliardini ◽

Nuno D. Pires ◽

...

Keyword(s):

Cell Proliferation ◽

Cell Lineage ◽

Embryonic Cell ◽

The Body ◽

Polycomb Group ◽

Normal Embryo ◽

Embryonic Patterning ◽

Polycomb Group Protein ◽

Group Protein

Establishing the body plan of a multicellular organism relies on precisely orchestrated cell divisions coupled with pattern formation. In animals, cell proliferation and embryonic patterning are regulated by Polycomb group (PcG) proteins that form various multisubunit complexes (Grossniklaus and Paro, 2014). The evolutionary conserved Polycomb Repressive Complex 2 (PRC2) trimethylates histone H3 at lysine 27 (H3K27me3) and comes in different flavors in the model plant Arabidopsis thaliana (Förderer et al., 2016; Grossniklaus and Paro, 2014). The histone methyltransferase MEDEA (MEA) is part of the FERTILIZATION INDEPENDENT SEED (FIS)-PRC2 required for seed development4. Although embryos derived from mea mutant egg cells show morphological abnormalities (Grossniklaus et al., 1998), defects in the development of the placenta-like endosperm are considered the main cause of seed abortion (Kinoshita et al., 1999; Scott et al., 1998), and a role of FIS-PRC2 in embryonic patterning was dismissed (Bouyer et al., 2011; Leroy et al., 2007). Here, we demonstrate that endosperm lacking MEA activity sustains normal embryo development and that embryos derived from mea mutant eggs abort even in presence of a wild-type endosperm because MEA is required for embryonic patterning and cell lineage determination. We show that, similar to PcG proteins in mammals, MEA regulates embryonic growth by repressing the transcription of core cell cycle components. Our work demonstrates that Arabidopsis embryogenesis is under epigenetic control of maternally expressed PcG proteins, revealing that PRC2 was independently recruited to control embryonic cell proliferation and patterning in animals and plants.

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Retinoic acid-induced proliferation of lung alveolar epithelial cells: relation with the IGF system

AJP Lung Cellular and Molecular Physiology ◽

10.1152/ajplung.1998.275.1.l71 ◽

1998 ◽

Vol 275 (1) ◽

pp. L71-L79 ◽

Cited By ~ 11

Author(s):

Elodie Nabeyrat ◽

Valérie Besnard ◽

Sophie Corroyer ◽

Véronique Cazals ◽

Annick Clement

Keyword(s):

Cell Proliferation ◽

Retinoic Acid ◽

Growth Factor ◽

Alveolar Epithelium ◽

Cell Number ◽

Dependent Manner ◽

Alveolar Epithelial ◽

Igf System ◽

Tgf Β1

Retinoids, including retinol and retinoic acid (RA) derivatives, are important molecules for lung growth and homeostasis. The presence of RA receptors and of RA-binding proteins in the alveolar epithelium led to suggest a role for RA on alveolar epithelial cell replication. In the present study, we examined the effects of RA on proliferation of the stem cells of the alveolar epithelium, the type 2 cells. We showed that treatment of serum-deprived type 2 cells with RA led to a stimulation of cell proliferation, with an increase in cell number in a dose-dependent manner. To gain some insights into the mechanisms involved, we studied the effects of RA on the expression of several components of the insulin-like growth factor (IGF) system that have been shown to be associated with the growth arrest of type 2 cells, mainly the IGF-binding protein-2 (IGFBP-2), IGF-II, and the type 2 IGF receptor. We documented a marked decrease in the expression of these components upon RA treatment. Using conditioned media from RA-treated cells, we provided evidence that the proliferative response of type 2 cells to RA was mediated through production of growth factor(s) distinct from IGF-I. We also showed that RA was able to reduce the decrease in cell number observed when type 2 cells were treated with transforming growth factor (TGF)-β1. These results together with the known stimulatory effect of TGF-β1 on IGFBP-2 expression led to suggest that RA may be associated with type 2 cell proliferation through mechanisms interfering with the TGF-β1 pathway.

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Planarian cell number depends on blitzschnell, a novel gene family that balances cell proliferation and cell death

Development ◽

10.1242/dev.184044 ◽

2020 ◽

Vol 147 (7) ◽

pp. dev184044 ◽

Cited By ~ 1

Author(s):

Eudald Pascual-Carreras ◽

Marta Marin-Barba ◽

Carlos Herrera-Úbeda ◽

Daniel Font-Martín ◽

Kay Eckelt ◽

...

Keyword(s):

Cell Proliferation ◽

Cell Death ◽

Gene Family ◽

Cell Number ◽

Novel Gene

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Cell lineage relationships in the development of the mammalian CNS: Role of cell lineage in control of cerebellar Purkinje cell number

Developmental Biology ◽

10.1016/0012-1606(86)90236-8 ◽

1986 ◽

Vol 115 (1) ◽

pp. 148-154 ◽

Cited By ~ 27

Author(s):

Karl Herrup

Keyword(s):

Purkinje Cell ◽

Cell Lineage ◽

Cell Number ◽

Cerebellar Purkinje Cell ◽

Mammalian Cns

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Does Heme Oxygenase-1 Have a Role in Caco-2 Cell Cycle Progression?

Experimental Biology and Medicine ◽

10.1177/15353702-0322805-52 ◽

2003 ◽

Vol 228 (5) ◽

pp. 590-595 ◽

Cited By ~ 13

Author(s):

Aliye Uc ◽

Bradley E. Britigan

Keyword(s):

Cell Cycle ◽

Cell Proliferation ◽

Renewal Process ◽

Cell Cycle Progression ◽

Intestinal Epithelial Cell ◽

Cell Number ◽

Heme Oxygenase 1 ◽

Intestinal Epithelial ◽

Cycle Progression ◽

Proliferation And Differentiation

Intestinal epithelium undergoes a rapid self-renewal process characterized by the proliferation of the crypt cells, their differentiation into mature enterocytes as they migrate up to the villi, followed by their shedding as they become senescent villus enterocytes. The exact mechanism that regulates the intestinal epithelium renewal process is not well understood, but the differential expression of regulatory genes along the crypt-villus axis may have a role. Heme oxygenase-1 (HO-1) is involved in endothelial cell cycle progression, but its role in the intestinal epithelial cell turnover has not been explored. With its effects on cell proliferation and its differential expression along the crypt-villus axis, HO-1 may play a role in the intestinal epithelial cell renewal process. In this study, we examined the role of HO-1 in the proliferation and differentiation of Caco-2 cells, a well-established in vitro model for human enterocytes. After confluence, Caco-2 cells undergo spontaneous differentiation and mimic the crypt to villus maturation observed in vivo. In preconfluent and confluent Caco-2 cells, HO-1 protein expression was determined with the immunoblot. HO-1 activity was determined by the ability of the enzyme to generate bilirubin from hemin. The effect of a HO-1 enzyme activity inhibitor, tin protoporphyrin (SnPP), on Caco-2 cell proliferation and differentiation was examined. In preconfluent cells, cell number was determined periodically as a marker of proliferation. Cell viability was measured with MTT assay. Cell differentiation was assessed by the expression of a brush border enzyme, alkaline phophatase (ALP). HO-1 was expressed in subconfluent Caco-2 cells and remained detectable until 2 days postconfluency. This timing was consistent with cells starting their differentiation and taking the features of normal intestinal epithelial cells. HO-1 was inducible in confluent Caco-2 cells by the enzyme substrate, hemin in a dose- and time-dependent manner. SnPP decreased the cell number and viability of preconfluent cells and delayed the ALP enzyme activity of confluent cells. HO-1 may be involved in intestinal cell cycle progression.

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