Growing an Embryo from a Single Cell: A Hurdle in Animal Life

doi:10.1101/CSHPERSPECT.A019042

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Growing an Embryo from a Single Cell: A Hurdle in Animal Life

Journal Article•DOI•

Growing an Embryo from a Single Cell: A Hurdle in Animal Life

Patrick H. O'Farrell¹•Institutions (1)

University of California, San Francisco¹

01 Nov 2015-Cold Spring Harbor Perspectives in Biology (Cold Spring Harbor Lab)-Vol. 7, Iss: 11

TL;DR: In mammals and in endoparasites, development in a nutritive environment releases the growth constraint, but growth of cells before gastrulation requires a new program to sustain pluripotency during this growth.

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Abstract: A requirement that an animal be able to feed to grow constrains how a cell can grow into an animal, and it forces an alternation between growth (increase in mass) and proliferation (increase in cell number). A growth-only phase that transforms a stem cell of ordinary proportions into a huge cell, the oocyte, requires dramatic adaptations to help a nucleus direct a 10(5)-fold expansion of cytoplasmic volume. Proliferation without growth transforms the huge egg into an embryo while still accommodating an impotent nucleus overwhelmed by the voluminous cytoplasm. This growth program characterizes animals that deposit their eggs externally, but it is changed in mammals and in endoparasites. In these organisms, development in a nutritive environment releases the growth constraint, but growth of cells before gastrulation requires a new program to sustain pluripotency during this growth.

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Nothing in Biology Makes Sense Except in the Light of Evolution

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Raghavendra Gadagkar

01 Nov 2005

TL;DR: The theory that biological species are descended from common ancestors provides an indispensable heuristic to understand why living organisms are what they are and do what they do.

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Abstract: Nothing in biology makes sense except in the light of evolution, quipped Theodosius Dobzhansky. The theory of evolution argues that each biological species was not suddenly and independently created but that all life forms are interrelated by virtue of having descended from common ancestors through the accumulation of modifications. Indeed, nothing we know about living organisms would make any sense if they were not so interrelated. And the theory that biological species are descended from common ancestors provides an indispensable heuristic to understand why living organisms are what they are and do what they do.

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974 citations

Journal Article•DOI•

Expression of engrailed proteins in arthropods, annelids and chordates

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N.H. Patel

01 Jan 1989-Trends in Genetics

TL;DR: A monoclonal antibody is described that recognizes a conserved epitope in the homeodomain of engrailed proteins of a number of different arthropods, annelids, and chordates; this antibody is used to isolate the grasshopperEngrailed gene, a homeobox gene that has an important role in Drosophila segmentation.

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582 citations

Journal Article•DOI•

Zygotic Genome Activation in Vertebrates.

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David Jukam¹, S. Ali M. Shariati¹, Jan M. Skotheim¹•Institutions (1)

Stanford University¹

21 Aug 2017-Developmental Cell

TL;DR: Progress in understanding vertebrate ZGA dynamics in frogs, fish, mice, and humans is reviewed to explore differences and emphasize common features.

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262 citations

Journal Article•DOI•

Waves of Cdk1 Activity in S Phase Synchronize the Cell Cycle in Drosophila Embryos

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Victoria E. Deneke¹, Anna Melbinger², Massimo Vergassola², Stefano Di Talia¹•Institutions (2)

Duke University¹, University of California, San Diego²

22 Aug 2016-Developmental Cell

TL;DR: In Drosophila embryos, Cdk1 positive feedback serves primarily to ensure the rapid onset of mitosis, while wave propagation is regulated by S phase events, demonstrating a fundamental distinction between S phase Cdk 1 waves, which propagate as active trigger waves in an excitable medium, and mitotic Cdk2 waves, who propagate as passive phase waves.

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118 citations

Journal Article•DOI•

Capturing Totipotent Stem Cells

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Christopher L. Baker, Martin F. Pera

04 Jan 2018-Cell Stem Cell

TL;DR: The biological and molecular characterization of cultured cells with developmental potential similar to totipotent blastomeres are reviewed, and recent progress toward the capture and stabilization of the totip powerless state in vitro is assessed.

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75 citations

Cites background from "Growing an Embryo from a Single Cel..."

...The existence of a regulative state of pluripotency throughout early development can be considered an innovation of mammalian evolution (Cañon et al., 2011; O’Farrell, 2015)....
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Journal Article•DOI•

Mitochondrial genome content is regulated during nematode development.

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William Y. Tsang¹, Bernard D. Lemire¹•Institutions (1)

Canadian Institutes of Health Research¹

15 Feb 2002-Biochemical and Biophysical Research Communications

TL;DR: In this paper, the authors measured the mtDNA copy number of each of the Caenorhabditis elegans developmental stages and found that the majority of mtDNA in adult worms are germline associated, and germline-deficient mutants show markedly reduced mtDNA contents.

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185 citations

Journal Article•DOI•

Activation of transcription in Drosophila embryos is a gradual process mediated by the nucleocytoplasmic ratio.

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D K Pritchard¹, G Schubiger•Institutions (1)

University of Washington¹

01 May 1996-Genes & Development

TL;DR: It is suggested that titration of transcription factors like ttk by the nucleocytoplasmic ratio triggers zygotic transcription in Drosophila.

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Abstract: We have observed that zygotic transcription does not initiate at a single point in Drosophila embryos. Rather, a gene initiates transcription in a few nuclei of a fraction of embryos. During succeeding cycles, the frequency of transcribing embryos, and of nuclei transcribing in those embryos, gradually increases. For the fushi tarazu (ftz) gene, the timing of this process is regulated by the concentration of the maternally loaded, repressing transcription factor tramtrack (ttk). Altering the dose of Ttk protein in embryos shifts the activation of ftz transcription either forward or backward during development but does not effect Kruppel (Kr) activation. We have observed that the transcription of several genes, including ftz, is triggered in embryos at a critical nuclear density; therefore, we suggest that titration of transcription factors like ttk by the nucleocytoplasmic ratio triggers zygotic transcription in Drosophila.

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183 citations

"Growing an Embryo from a Single Cel..." refers background in this paper

...The slowing of the cell cycle, MZT, and onset of the cell-shape changes and movements that initiate morphogenesis occur over a relatively short time span that is called the midblastula transition (MBT) (Farrell and O’Farrell 2014)....
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...Although it is not yet understood how the MBT is controlled, it seems natural to believe that the embryo is running out of something— perhaps a key component is used up, or a maternal supply becomes inadequate as nuclei increase....
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...For example, inhibitory phosphorylation leads to a decline in activity of the cell-cycle kinase, Cdk1, prolongs S phase, and introduces a G2 phase at the MBT in Drosophila (Edgar and O’Farrell 1990; Farrell and O’Farrell 2013)....
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...Experimental manipulation of the ratio of nuclei to cytoplasm suggests that its increase has an input into the MBT (Newport and Kirschner 1982a,b; Edgar and Schubiger 1986; Edgar et al. 1986; Pritchard and Schubiger 1996)....
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...Phosphorylation of nucleoplasmin persists until the MBT is dependent on high-cyclin-dependent kinase activity, a specialization of the proliferation-only phase....
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Journal Article•DOI•

Identification of a developmental timer regulating the stability of embryonic cyclin A and a new somatic A-type cyclin at gastrulation.

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John A. Howe¹, Michael Howell, Tim Hunt, John W. Newport•Institutions (1)

University of California, San Diego¹

15 May 1995-Genes & Development

TL;DR: The observations suggest that a previously uncharacterized timing mechanism activates new degradative pathways at the onset of gastrulation, which could play an essential role in releasing cells from maternal programming.

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Abstract: We have identified a second Xenopus cyclin A, called cyclin A2. Cyclin A2 is a 46.6-kD protein that shows a greater homology to human cyclin A than to the previously identified Xenopus cyclin A1. It is present throughout embryonic development (up to stage 46 at least) and is found in adult tissues as well as in Xenopus tissue culture cell lines. In contrast, cyclin A1 is present in eggs and early embryos but cannot be detected in late embryos or in tissue culture cells. We have found that the maternally stored pools of mRNAs encoding both of these cyclin A proteins are stable until the onset of gastrulation and then are degraded abruptly. At this time, new transcription replaces cyclin A2 mRNA. Interestingly, we have also observed a dramatic change in the stability of the cyclin A proteins at this time. Prior to the onset of gastrulation, cyclin A1 protein is stable during interphase of the cell cycle. At gastrulation, however, both A1 and A2 proteins turn over rapidly during interphase of the cell cycle. Together, these results indicate that developmental programs controlling cyclin A protein and mRNA stability are activated at gastrulation. We have shown that this program is independent of new transcription beginning at the mid-blastula transition. Furthermore, treatment of early stage embryos with cycloheximide demonstrates that activation of this degradative program is independent of cell division and translation. Collectively, our observations suggest that a previously uncharacterized timing mechanism activates new degradative pathways at the onset of gastrulation, which could play an essential role in releasing cells from maternal programming.

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172 citations

"Growing an Embryo from a Single Cel..." refers background in this paper

...Additionally, hydroxyurea does not block the early S phases of Xenopus or of Drosophila (Landström et al. 1975; Newport and Dasso 1989; Howe et al. 1995; K Yuan, AW Shermoen, PH O’Farrell, unpubl.)....
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Journal Article•DOI•

Developmental activation of the Rb-E2F pathway and establishment of cell cycle-regulated cyclin-dependent kinase activity during embryonic stem cell differentiation.

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Josephine White¹, Elaine Stead¹, Renate Faast¹, Simon J. Conn¹, Peter Cartwright¹, Stephen Dalton¹, Stephen Dalton² - Show less +3 more•Institutions (2)

University of Adelaide¹, University of Georgia²

01 Apr 2005-Molecular Biology of the Cell

TL;DR: The results suggest the existence of a feedback loop where Cdk2 controls its own activity through regulation of cyclin E1 transcription, which can be explained by activation of the E2F-pRb pathway.

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Abstract: To understand cell cycle control mechanisms in early development and how they change during differentiation, we used embryonic stem cells to model embryonic events. Our results demonstrate that as pluripotent cells differentiate, the length of G(1) phase increases substantially. At the molecular level, this is associated with a significant change in the size of active cyclin-dependent kinase (Cdk) complexes, the establishment of cell cycle-regulated Cdk2 activity and the activation of a functional Rb-E2F pathway. The switch from constitutive to cell cycle-dependent Cdk2 activity coincides with temporal changes in cyclin A2 and E1 protein levels during the cell cycle. Transcriptional mechanisms underpin the down-regulation of cyclin levels and the establishment of their periodicity during differentiation. As pluripotent cells differentiate and pRb/p107 kinase activities become cell cycle dependent, the E2F-pRb pathway is activated and imposes cell cycle-regulated transcriptional control on E2F target genes, such as cyclin E1. These results suggest the existence of a feedback loop where Cdk2 controls its own activity through regulation of cyclin E1 transcription. Changes in rates of cell division, cell cycle structure and the establishment of cell cycle-regulated Cdk2 activity can therefore be explained by activation of the E2F-pRb pathway.

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167 citations

"Growing an Embryo from a Single Cel..." refers background in this paper

...During G1, the canonical regulators of progress to S phase, Rb, and cyclin E, are inappropriately phosphorylated and abundant, respectively (White et al. 2005)....
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Journal Article•DOI•

From Egg to Gastrula: How the Cell Cycle Is Remodeled During the Drosophila Mid-Blastula Transition

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Jeffrey A. Farrell¹, Patrick H. O'Farrell¹•Institutions (1)

Harvard University¹

24 Nov 2014-Annual Review of Genetics

TL;DR: The core mechanisms of the change in cell cycle regulation are reviewed, advances in understanding of how these might be timed and triggered are discussed, and how the elements of this program may be conserved or changed in other organisms are considered.

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Abstract: Many, if not most, embryos begin development with extremely short cell cycles that exhibit unusually rapid DNA replication and no gap phases. The commitment to the cell cycle in the early embryo appears to preclude many other cellular processes that only emerge as the cell cycle slows just prior to gastrulation at a major embryonic transition known as the mid-blastula transition (MBT). As reviewed here, genetic and molecular studies in Drosophila have identified changes that extend S phase and introduce a post-replicative gap phase, G2, to slow the cell cycle. Although many mysteries remain about the upstream regulators of these changes, we review the core mechanisms of the change in cell cycle regulation and discuss advances in our understanding of how these might be timed and triggered. Finally, we consider how the elements of this program may be conserved or changed in other organisms.

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163 citations

"Growing an Embryo from a Single Cel..." refers background in this paper

...Shortening of S phase by as much as 100- fold further quickens these cycles (Farrell and O’Farrell 2014)....
[...]
...The slowing of the cell cycle, MZT, and onset of the cell-shape changes and movements that initiate morphogenesis occur over a relatively short time span that is called the midblastula transition (MBT) (Farrell and O’Farrell 2014)....
[...]
...Although it is not yet understood how the MBT is controlled, it seems natural to believe that the embryo is running out of something— perhaps a key component is used up, or a maternal supply becomes inadequate as nuclei increase....
[...]
...For example, inhibitory phosphorylation leads to a decline in activity of the cell-cycle kinase, Cdk1, prolongs S phase, and introduces a G2 phase at the MBT in Drosophila (Edgar and O’Farrell 1990; Farrell and O’Farrell 2013)....
[...]
...Experimental manipulation of the ratio of nuclei to cytoplasm suggests that its increase has an input into the MBT (Newport and Kirschner 1982a,b; Edgar and Schubiger 1986; Edgar et al. 1986; Pritchard and Schubiger 1996)....
[...]