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: The study of the vertebrate anteroposterior axis forms through elongation of multiple tissues during embryogenesis is likely to shed light on the cross talk between signaling and mechanics during morphogenesis.
Abstract: The vertebrate anteroposterior axis forms through elongation of multiple tissues during embryogenesis. This process is based on tissue-autonomous mechanisms of force generation and intertissue mechanical coupling whose failure leads to severe developmental anomalies such as body truncation and spina bifida. Similar to other morphogenetic modules, anteroposterior body extension requires both the rearrangement of existing materials-such as cells and extracellular matrix-and the local addition of new materials, i.e., anisotropic growth, through cell proliferation, cell growth, and matrix deposition. Numerous signaling pathways coordinate body axis formation via regulation of cell behavior during tissue rearrangements and/or volumetric growth. From a physical perspective, morphogenesis depends on both cell-generated forces and tissue material properties. As the spatiotemporal variation of these mechanical parameters has recently been explored in the context of vertebrate body elongation, the study of this process is likely to shed light on the cross talk between signaling and mechanics during morphogenesis.
36 citations
TL;DR: This review argues that studying the regulation of the cell cycle in early embryonic development will reveal novel principles of how embryos accurately measure time and compares the development of flies to that of other metazoans.
33 citations
TL;DR: Surprisingly, it was found that U7 base-pairing with nascent histone transcripts was not required for localization to HLBs, and this data support a model in which transcription of specific gene loci nucleates nuclear body components with high specificity and fidelity to perform distinct regulatory functions.
Abstract: Nuclear bodies are cellular compartments that lack lipid bilayers and harbor specific RNAs and proteins. Recent proposals that nuclear bodies form through liquid-liquid phase separation leave the question of how different nuclear bodies maintain their distinct identities unanswered. Here we investigate Cajal bodies (CBs), histone locus bodies (HLBs) and nucleoli - involved in assembly of the splicing machinery, histone mRNA 3' end processing, and rRNA processing, respectively - in the embryos of the zebrafish, Danio rerio. We take advantage of the transcriptional silence of the 1-cell embryo and follow nuclear body appearance as zygotic transcription becomes activated. CBs are present from fertilization onwards, while HLB and nucleolar components formed foci several hours later when histone genes and rDNA became active. HLB formation was blocked by transcription inhibition, suggesting nascent histone transcripts recruit HLB components like U7 snRNP. Surprisingly, we found that U7 base-pairing with nascent histone transcripts was not required for localization to HLBs. Rather, the type of Sm ring assembled on U7 determined its targeting to HLBs or CBs; the spliceosomal Sm ring targeted snRNAs to CBs while the specialized U7 Sm-ring localized to HLBs, demonstrating the contribution of protein constituents to the distinction among nuclear bodies. Thus, nucleolar, HLB, and CB components can mix in early embryogenesis when transcription is naturally or artificially silenced. These data support a model in which transcription of specific gene loci nucleates nuclear body components with high specificity and fidelity to perform distinct regulatory functions.
32 citations
TL;DR: This work compares fixed-time to on-the-fly decisions, based on comparing the likelihoods of anterior/posterior locations, and finds that these more efficient schemes complete reliable cell fate decisions within the short embryological timescales.
Abstract: Cell fate decisions in the fly embryo are rapid: hunchback genes decide in minutes whether nuclei follow the anterior/posterior developmental blueprint by reading out positional information in the Bicoid morphogen. This developmental system is a prototype of regulatory decision processes that combine speed and accuracy. Traditional arguments based on fixed-time sampling of Bicoid concentration indicate that an accurate readout is impossible within the experimental times. This raises the general issue of how speed-accuracy tradeoffs are achieved. Here, we compare fixed-time to on-the-fly decisions, based on comparing the likelihoods of anterior/posterior locations. We found that these more efficient schemes complete reliable cell fate decisions within the short embryological timescales. We discuss the influence of promoter architectures on decision times and error rates, present concrete examples that rapidly readout the morphogen, and predictions for new experiments. Lastly, we suggest a simple mechanism for RNA production and degradation that approximates the log-likelihood function.
26 citations
TL;DR: Embryos that were arrested two cell cycles prior to the normal MBT activated widespread transcription of the zygotic genome including genes previously described as N/C dependent, and zygotically regulated post-MBT events such as cellularization and gastrulation movements occurred in these cell cycle–arrested embryos.
Abstract: Externally deposited eggs begin development with an immense cytoplasm and a single overwhelmed nucleus. Rapid mitotic cycles restore normality as the ratio of nuclei to cytoplasm (N/C) increases. A threshold N/C has been widely proposed to activate zygotic genome transcription and onset of morphogenesis at the mid-blastula transition (MBT). To test whether a threshold N/C is required for these events, we blocked N/C increase by down-regulating cyclin/Cdk1 to arrest early cell cycles in Drosophila. Embryos that were arrested two cell cycles prior to the normal MBT activated widespread transcription of the zygotic genome including genes previously described as N/C dependent. Zygotic transcription of these genes largely retained features of their regulation in space and time. Furthermore, zygotically regulated post-MBT events such as cellularization and gastrulation movements occurred in these cell cycle-arrested embryos. These results are not compatible with models suggesting that these MBT events are directly coupled to N/C. Cyclin/Cdk1 activity normally declines in tight association with increasing N/C and is regulated by N/C. By experimentally promoting the decrease in cyclin/Cdk1, we uncoupled MBT from N/C increase, arguing that N/C-guided down-regulation of cyclin/Cdk1 is sufficient for genome activation and MBT.
21 citations
Cites background from "Growing an Embryo from a Single Cel..."
...Unlike mammalian eggs, whose growth and development is fostered in a nutrient-rich environment, the ancestral and common program of development requires eggs that provide for external development into free-living organisms [1, 2]....
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...The egg, with its single diploid nucleus, does not have the capacity to rapidly adjust the population of transcripts in its huge cytoplasm [2, 3]....
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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