Growing an Embryo from a Single Cell: A Hurdle in Animal Life
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.
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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TL;DR: Elongation of the vertebrate body axis by posterior volumetric growth is linked to increased energy supply and is absent from the externally developing zebrafish embryo.
Abstract: Posterior body elongation is a widespread mechanism propelling the generation of the metazoan body plan. The posterior growth model predicts that a posterior growth zone generates sufficient tissue volume to elongate the posterior body. However, there are energy supply-related differences between vertebrates in the degree to which growth occurs concomitantly with embryogenesis. By applying a multi-scalar morphometric analysis in zebrafish embryos, we show that posterior body elongation is generated by an influx of cells from lateral regions, by convergence-extension of cells as they exit the tailbud, and finally by a late volumetric growth in the spinal cord and notochord. Importantly, the unsegmented region does not generate additional tissue volume. Fibroblast growth factor inhibition blocks tissue convergence rather than volumetric growth, showing that a conserved molecular mechanism can control convergent morphogenesis through different cell behaviours. Finally, via a comparative morphometric analysis in lamprey, dogfish, zebrafish and mouse, we propose that elongation via posterior volumetric growth is linked to increased energy supply and is associated with an overall increase in volumetric growth and elongation.
75 citations
Cites background from "Growing an Embryo from a Single Cel..."
...…for convergence and extension, but not posterior volumetric growth in zebrafish FGF signalling is known to be important for posterior body elongation across vertebrates (Bénazéraf et al., 2010; Bouldin et al., 2014; del Corral and Storey, 2004; Olivera-Martinez et al., 2012; Lawton et al., 2013)....
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TL;DR: An outline of the mechanisms slowing the cell cycle at and around the time of MBT is provided to provide a guiding paradigm for the study of other MBT changes as the embryo transits from maternal control to a regulatory program centered on the expression of zygotic genes.
70 citations
Cites background from "Growing an Embryo from a Single Cel..."
...While not discussed here, mammalian embryogenesis in its protected and nutritious uterine environment is derived from the ancestral programs discussed here [1,4]....
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...This restriction necessitates the ‘big egg’ program in which the egg is loaded with everything needed to fund the development of a feeding-competent organism [1]....
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TL;DR: The germ track is the cellular path by which genes are transmitted to future generations whereas somatic cells die with their body and do not leave direct descendants, so the performance of most bodily functions by a sequestered soma reduces organismal costs of TEs.
Abstract: The germ track is the cellular path by which genes are transmitted to future generations whereas somatic cells die with their body and do not leave direct descendants. Transposable elements (TEs) evolve to be silent in somatic cells but active in the germ track. Thus, the performance of most bodily functions by a sequestered soma reduces organismal costs of TEs. Flexible forms of gene regulation are permissible in the soma because of the self-imposed silence of TEs, but strict licensing of transcription and translation is maintained in the germ track to control proliferation of TEs. Delayed zygotic genome activation (ZGA) and maternally inherited germ granules are adaptations that enhance germ-track security. Mammalian embryos exhibit very early ZGA associated with extensive mobilization of retroelements. This window of vulnerability to retrotransposition in early embryos is an indirect consequence of evolutionary conflicts within the mammalian genome over postzygotic maternal provisioning.
60 citations
Cites background from "Growing an Embryo from a Single Cel..."
...undoubtedly related to the replacement of yolk-based oviparity by placental viviparity [17, 19]....
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TL;DR: It is proposed that the high energetic cost of cell-cycle signaling reflects the significant thermodynamic burden of imposing accurate and robust timing on cell proliferation during development.
54 citations
TL;DR: This analysis bears upon the inhibition required to suppress Cdk1 waves at the cell-cycle pause for the maternal-to-zygotic transition and generates a wave-like spreading that differs from bistable waves for its dependence on dynamic parameters and its faster speed.
Abstract: Early embryogenesis of most metazoans is characterized by rapid and synchronous cleavage divisions. Chemical waves of Cdk1 activity were previously shown to spread across Drosophila embryos, and the underlying molecular processes were dissected. Here, we present the theory of the physical mechanisms that control Cdk1 waves in Drosophila. The in vivo dynamics of Cdk1 are captured by a transiently bistable reaction–diffusion model, where time-dependent reaction terms account for the growing level of cyclins and Cdk1 activation across the cell cycle. We identify two distinct regimes. The first one is observed in mutants of the mitotic switch. There, waves are triggered by the classical mechanism of a stable state invading a metastable one. Conversely, waves in wild type reflect a transient phase that preserves the Cdk1 spatial gradients while the overall level of Cdk1 activity is swept upward by the time-dependent reaction terms. This unique mechanism generates a wave-like spreading that differs from bistable waves for its dependence on dynamic parameters and its faster speed. Namely, the speed of “sweep” waves strikingly decreases as the strength of the reaction terms increases and scales as the powers 3/4, −1/2, and 7/12 of Cdk1 molecular diffusivity, noise amplitude, and rate of increase of Cdk1 activity in the cell-cycle S phase, respectively. Theoretical predictions are supported by numerical simulations and experiments that couple quantitative measurements of Cdk1 activity and genetic perturbations of the accumulation rate of cyclins. Finally, our analysis bears upon the inhibition required to suppress Cdk1 waves at the cell-cycle pause for the maternal-to-zygotic transition.
53 citations
References
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TL;DR: Induction of pluripotent stem cells from mouse embryonic or adult fibroblasts by introducing four factors, Oct3/4, Sox2, c-Myc, and Klf4, under ES cell culture conditions is demonstrated and iPS cells, designated iPS, exhibit the morphology and growth properties of ES cells and express ES cell marker genes.
23,959 citations
"Growing an Embryo from a Single Cel..." refers background in this paper
...Tremendous advances in the study of stem cells have identified mammalian factors that can reprogram differentiated cells to pluripotency (Takahashi and Yamanaka 2006)....
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TL;DR: The establishment in tissue culture of pluripotent cell lines which have been isolated directly from in vitro cultures of mouse blastocysts are reported, able to differentiate either in vitro or after innoculation into a mouse as a tumour in vivo.
Abstract: Pluripotential cells are present in a mouse embryo until at least an early post-implantation stage, as shown by their ability to take part hi the formation of chimaeric animals1 and to form teratocarcinomas2. Until now it has not been possible to establish progressively growing cultures of these cells in vitro, and cell lines have only been obtained after teratocarcinoma formation in vivo. We report here the establishment in tissue culture of pluripotent cell lines which have been isolated directly from in vitro cultures of mouse blastocysts. These cells are able to differentiate either in vitro or after innoculation into a mouse as a tumour in vivo. They have a normal karyotype.
8,144 citations
TL;DR: In this article, the authors described the establishment directly from normal preimplantation mouse embryos of a cell line that forms teratocarcinomas when injected into mice and demonstrated the pluripotency of these embryonic stem cells by the observation that subclonal cultures, derived from isolated single cells, can differentiate into a wide variety of cell types.
Abstract: This report describes the establishment directly from normal preimplantation mouse embryos of a cell line that forms teratocarcinomas when injected into mice. The pluripotency of these embryonic stem cells was demonstrated conclusively by the observation that subclonal cultures, derived from isolated single cells, can differentiate into a wide variety of cell types. Such embryonic stem cells were isolated from inner cell masses of late blastocysts cultured in medium conditioned by an established teratocarcinoma stem cell line. This suggests that such conditioned medium might contain a growth factor that stimulates the proliferation or inhibits the differentiation of normal pluripotent embryonic cells, or both. This method of obtaining embryonic stem cells makes feasible the isolation of pluripotent cells lines from various types of noninbred embryo, including those carrying mutant genes. The availability of such cell lines should made possible new approaches to the study of early mammalian development.
5,496 citations
TL;DR: The Copernican world model has been shown to be a "mere theory" as mentioned in this paper, not a "fact," and it has not been verified by direct observations even to the extent the sphericity of the earth has been observed.
Abstract: As RECENTLY AS 1966, sheik Abd el Aziz bin Baz asked the king of Saudi Arabia to suppress a heresy that was spreading in his land. Wrote the sheik: "The Holy Koran, the Prophet's teachings, the majority of Islamic scientists, and the actual facts all prove that the sun is running in its orbit ... and that the earth is fixed and stable, spread out by God for his mankind. ... Anyone who professed otherwise would utter a charge of falsehood toward God, the Koran, and the Prophet." The good sheik evidently holds the Copernican theory to be a "mere theory," not a "fact." In this he is technically correct. A theory can be verified by a mass of facts, but it becomes a proven theory, not a fact. The sheik was perhaps unaware that the Space Age had begun before he asked the king to suppress the Copernican heresy. The sphericity of the earth had been seen by astronauts, and even by many earth-bound people on their television screens. Perhaps the sheik could retort that those who venture beyond the confines of God's earth suffer hallucinations, and that the earth is really flat. Parts of the Copernican world model, such as the contention that the earth rotates around the sun, and not vice versa, have not been verified by direct observations even to the extent the sphericity of the earth has been. Yet scientists accept the model as an accurate representation of reality. Why? Because it makes sense of a multitude of facts which are otherwise meaningless or extravagant. To nonspecialists most of these facts are unfamiliar. Why then do we accept the "mere theory" that the earth is a sphere revolving around a spherical sun? Are we simply submitting to authority? Not quite: we know that those who took time to study the evidence found it convincing. The good sheik is probably ignorant of the evidence. Even more likely, he is so hopelessly biased that no amount of evidence would impress him. Anyway, it would be sheer waste of time to attempt to convince him. The Koran and the Bible do not contradict Copernicus, nor does Copernicus contradict them. It is ludicrous to mistake the Bible and the Koran for primers of natural science. They treat of matters even more important: the meaning of man and his relations to God. They are written in poetic symbols that were understandable to people of the age when they were written, as well as to peoples of all other ages. The king of Arabia did not comply with the sheik's demand. He knew that some people fear enlightenment, because enlightenment threatens their vested interests. Education is not to be used to promote obscurantism. The earth is not the geometric center of the universe, although it may be its spiritual center. It is a mere speck of dust in cosmic spaces. Contrary to Bishop Ussher's calculations, the world did not appear in approximately its present state in 4004 B.C. The estimates of the age of the universe given by modern cosmologists are still only rough approximations, which are revised (usually upward) as the methods of estimation are refined. Some cosmologists take the universe to be about 10 billion years old; others suppose that it may have existed, and will continue to exist, eternally. The origin of life on earth is dated tentatively between 3 and 5 billion years ago; manlike beings appeared relatively quite recently, between 2 and 4 million years ago. The estimates of the age of the earth, of the duration of the geologic and paleontologic eras, and of the antiquity of man's ancestors are now based mainly on radiometric evidence-the proportions of isotopes of certain chemical elements in rocks suitable for such studies.
2,143 citations
TL;DR: The Xenopus embryo undergoes 12 rapid synchronous cleavages followed by a period of slower asynchronous divisions more typical of somatic cells, termed the midblastula transition (MBT), which shows that at the MBT the blastomeres become motile and transcriptionally active for the first time.
1,587 citations