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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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.
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.
974 citations
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.
Abstract: engrailed is a homeobox gene that has an important role in Drosophila segmentation. Genes homologous to engrailed have been identified in several other organisms. Here we describe a monoclonal antibody that recognizes a conserved epitope in the homeodomain of engrailed proteins of a number of different arthropods, annelids, and chordates; we use this antibody to isolate the grasshopper engrailed gene. In Drosophila embryos, the antibody reveals engrailed protein in the posterior portion of each segment during segmentation, and in a segmentally reiterated subset of neuronal cells during neurogenesis. Other arthropods, including grasshopper and two crustaceans, have similar patterns of engrailed expression. However, these patterns of expression are not shared by the annelids or chordates we examined. Our results provide the most comprehensive view that has been obtained of how expression patterns of a regulatory gene vary during evolution. On the basis of these patterns, we suggest that engrailed is a gene whose ancestral function was in neurogenesis and whose function was co-opted during the evolution of segmentation in the arthropods, but not in the annelids and chordates.
582 citations
TL;DR: Progress in understanding vertebrate ZGA dynamics in frogs, fish, mice, and humans is reviewed to explore differences and emphasize common features.
Abstract: The first major developmental transition in vertebrate embryos is the maternal-to-zygotic transition (MZT) when maternal mRNAs are degraded and zygotic transcription begins. During the MZT, the embryo takes charge of gene expression to control cell differentiation and further development. This spectacular organismal transition requires nuclear reprogramming and the initiation of RNAPII at thousands of promoters. Zygotic genome activation (ZGA) is mechanistically coordinated with other embryonic events, including changes in the cell cycle, chromatin state, and nuclear-to-cytoplasmic component ratios. Here, we review progress in understanding vertebrate ZGA dynamics in frogs, fish, mice, and humans to explore differences and emphasize common features.
262 citations
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.
Abstract: Embryos of most metazoans undergo rapid and synchronous cell cycles following fertilization. While diffusion is too slow for synchronization of mitosis across large spatial scales, waves of Cdk1 activity represent a possible process of synchronization. However, the mechanisms regulating Cdk1 waves during embryonic development remain poorly understood. Using biosensors of Cdk1 and Chk1 activities, we dissect the regulation of Cdk1 waves in the Drosophila syncytial blastoderm. We show that Cdk1 waves are not controlled by the mitotic switch but by a double-negative feedback between Cdk1 and Chk1. Using mathematical modeling and surgical ligations, we demonstrate a fundamental distinction between S phase Cdk1 waves, which propagate as active trigger waves in an excitable medium, and mitotic Cdk1 waves, which propagate as passive phase waves. Our findings show that in Drosophila embryos, Cdk1 positive feedback serves primarily to ensure the rapid onset of mitosis, while wave propagation is regulated by S phase events.
118 citations
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.
Abstract: Minority subpopulations within embryonic stem cell cultures display an expanded developmental potential similar to that of early embryo blastomeres or the early inner cell mass. The ability to isolate and culture totipotent cells capable of giving rise to the entire conceptus would enhance our capacity to study early embryo development, and might enable more efficient generation of chimeric animals for research and organ production for transplantation. Here we review the biological and molecular characterization of cultured cells with developmental potential similar to totipotent blastomeres, and assess recent progress toward the capture and stabilization of the totipotent state in vitro.
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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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.
Abstract: Differentiated cells can be reprogrammed to an embryonic-like state by transfer of nuclear contents into oocytes or by fusion with embryonic stem (ES) cells. Little is known about factors that induce this reprogramming. Here, we demonstrate 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. Unexpectedly, Nanog was dispensable. These cells, which we designated iPS (induced pluripotent stem) cells, exhibit the morphology and growth properties of ES cells and express ES cell marker genes. Subcutaneous transplantation of iPS cells into nude mice resulted in tumors containing a variety of tissues from all three germ layers. Following injection into blastocysts, iPS cells contributed to mouse embryonic development. These data demonstrate that pluripotent stem cells can be directly generated from fibroblast cultures by the addition of only a few defined factors.
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.
Abstract: The Xenopus embryo undergoes 12 rapid synchronous cleavages followed by a period of slower asynchronous divisions more typical of somatic cells. This change in cell cleavage has been termed the midblastula transition (MBT). We show that at the MBT the blastomeres become motile and transcriptionally active for the first time. We have investigated the timing of the MBT and found that it does not depend on cell division, on time since fertilization or on a counting mechanism involving the sequential modification of DNA. Rather, the timing of the MBT depends on reaching a critical ratio of nucleus to cytoplasm. We view the MBT as a consequence of the titration of some substance, originally present in the egg, by the exponentially increasing nuclear material. When this substance is exhausted a new cell program is engaged, leading to the acquisition of several new cell properties.
1,587 citations