Mystery at the heart of life

_{Denyse O'Leary

December 21, 2014

Cell biology, Intelligent Design, News

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Cell biology
Intelligent Design
News}

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By Biologic Institute’s Ann Gauger, at Christianity Today’s Behemoth, the secret life of cells:

Our bodies are made up of some 100 trillion cells. We tend to think of cells as static, because that’s how they were presented to us in textbooks. In fact, the cell is like the most antic, madcap, crowded (yet fantastically efficient) city you can picture. And at its heart lies a mystery—or I should say, several mysteries—involving three special kinds of molecules: DNA, RNA, and proteins.

These molecules are assembled into long chains called polymers, and are uniquely suited for the roles they play. More importantly, life absolutely depends upon them. We have to have DNA, RNA, and protein all present and active at the same time for a living organism to live.

How they work together so optimally and efficiently is not merely amazing, but also a great enigma, a mystery that lies at the heart of life itself. More. Paywall soon after. May be worth it.

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Comments

[...] non-protein-coding sequences house a set of information-rich instructions, many of which are likely to be regulatory in nature and transacted as RNA species, which have facilitated the emergence of biological complexity. [...] the protein-coding repertoire has changed little since the dawn of multicellularity [...] [...] there is a substantial problem of “missing information” that can be resolved if non-protein-coding sequences are as information rich [...] [...] the mammalian genome is nearly maximized with regulatory information bound within ncDNA.
A meta-analysis of the genomic and transcriptomic composition of complex life Ganqiang Liu, 1 , 2 John S. Mattick, 2 and Ryan J. Taft Cell Cycle. 12(13): 2061–2072. doi: 10.4161/cc.25134

Complex complexityDionisio_{July 10, 2017
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(1) the number of protein-coding genes and bases does not scale with biological complexity and is in fact relatively static across all multicellular animal lineages; (2) there is a strong and statistically significant correlation between the proportion of the genome that is non-protein-coding and organismal complexity; (3) a meta-analysis of more than 170 RNA-seq data sets has revealed, consistent with other studies,4-8 that the vast majority of multicellular animal genomes are transcribed.
A meta-analysis of the genomic and transcriptomic composition of complex life Ganqiang Liu, 1 , 2 John S. Mattick, 2 and Ryan J. Taft Cell Cycle. 12(13): 2061–2072. doi: 10.4161/cc.25134

Complex complexityDionisio_{July 10, 2017
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It is now clear that animal genomes are predominantly non-protein-coding, and that these sequences encode a wide array of RNA transcripts and other regulatory elements that are fundamental to the development of complex life. [...] the proportion of an animal genome that is non-protein-coding DNA (ncDNA) correlates well with its apparent biological complexity. [...] ncDNA, and the ncRNAs encoded within it, may be intimately involved in the evolution, maintenance and development of complex life.
A meta-analysis of the genomic and transcriptomic composition of complex life Ganqiang Liu, 1 , 2 John S. Mattick, 2 and Ryan J. Taft Cell Cycle. 12(13): 2061–2072. doi: 10.4161/cc.25134

Some archaic pseudoscientific hogwash in an otherwise interesting paper. Complex complexityDionisio_{July 10, 2017
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The kinetochore and checkpoint proteins form a complex set of interactions that facilitate the generation of the ‘wait anaphase' signal in the form of the MCC. Understanding SAC signalling requires the elucidation of the molecular interactions between checkpoint components.
Bub1 positions Mad1 close to KNL1 MELT repeats to promote checkpoint signalling Gang Zhang,a,1 Thomas Kruse,1 Blanca López-Méndez,1 Kathrine Beck Sylvestersen,1 Dimitriya H. Garvanska,1 Simone Schopper,1 Michael Lund Nielsen,1 and Jakob Nilsson Nat Commun. 2017; 8: 15822. doi: 10.1038/ncomms15822

Complex complexityDionisio_{July 10, 2017
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Proper segregation of chromosomes depends on a functional spindle assembly checkpoint (SAC) and requires kinetochore localization of the Bub1 and Mad1/Mad2 checkpoint proteins. Several aspects of Mad1/Mad2 kinetochore recruitment in human cells are unclear and in particular the underlying direct interactions. This work dissects functionally relevant molecular interactions required for spindle assembly checkpoint signalling at kinetochores in human cells.
Bub1 positions Mad1 close to KNL1 MELT repeats to promote checkpoint signalling Gang Zhang,a,1 Thomas Kruse,1 Blanca López-Méndez,1 Kathrine Beck Sylvestersen,1 Dimitriya H. Garvanska,1 Simone Schopper,1 Michael Lund Nielsen,1 and Jakob Nilsson Nat Commun. 2017; 8: 15822. doi: 10.1038/ncomms15822

Complex complexityDionisio_{July 10, 2017
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The validity of the induction model should be investigated further [...] [...] more observational data are required to understand the developmental functions of eyespot organisers and differentiating epithelial cells in general in butterfly wing tissues.
Butterfly eyespot organiser: in vivo imaging of the prospective focal cells in pupal wing tissues Mayo Iwasaki,1 Yoshikazu Ohno,1 and Joji M. Otaki Sci Rep. 2017; 7: 40705. doi: 10.1038/srep40705

Complex complexityDionisio_{July 6, 2017
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An organiser is a cluster of cells that can induce differentiation of their surrounding cells, and many molecules that are critically involved in the induction process have been identified. Their molecular network is fairly complex.
Butterfly eyespot organiser: in vivo imaging of the prospective focal cells in pupal wing tissues Mayo Iwasaki,1 Yoshikazu Ohno,1 and Joji M. Otaki Sci Rep. 2017; 7: 40705. doi: 10.1038/srep40705

Complex complexityDionisio_{July 6, 2017
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[...] organiser cells are developmentally ahead of cells in other regions and that position-dependent heterochronic development is a general mechanism for constructing colour patterns in butterfly wings.
Butterfly eyespot organiser: in vivo imaging of the prospective focal cells in pupal wing tissues Mayo Iwasaki,1 Yoshikazu Ohno,1 and Joji M. Otaki Sci Rep. 2017; 7: 40705. doi: 10.1038/srep40705

Complex complexityDionisio_{July 6, 2017
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The controlled generation of a Wnt gradient by cytonemes is a prerequisite to establishing a morphogenetic Wnt field that allows precise tissue patterning, such as in the vertebrate neural plate. [...] the next step is to substantiate our understanding of the molecular mechanisms that control the formation of these signaling filopodia. [...] it is crucial to determine whether other ligands in the Wnt pathway use a similar distribution mechanism. [...] it is important to investigate whether other delivery mechanisms, in addition to those relying on cytonemes, are used in parallel or whether there is a strict tissue-dependency for the specific transport mechanism employed. [...] further research is needed before extracellular Wnt trafficking, its impact on morphogenetic gradient formation and the effect on tissue patterning are fully understood.
Role of cytonemes in Wnt transport. Stanganello E, Scholpp S J Cell Sci. 129(4):665-72. doi: 10.1242/jcs.182469

Complex complexityDionisio_{July 5, 2017
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Wnt proteins might be transported through multi-protein complexes that mask their hydrophobic lipid modifications and increase solubility. [...] exovesicles have been proposed to play a role in the passage of hydrophobic Wnt molecules through tissue [...] the delivery mode of Wnt proteins in the stem cell niche remains to be elucidated. It is, therefore, important to analyze any context-dependency on the characteristics of cytonemes and the mechanisms of transport.
Role of cytonemes in Wnt transport. Stanganello E, Scholpp S J Cell Sci. 129(4):665-72. doi: 10.1242/jcs.182469

Complex complexityDionisio_{July 5, 2017
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[...] long-range spreading of Wnt proteins by diffusion is unlikely [...]
Role of cytonemes in Wnt transport. Stanganello E, Scholpp S J Cell Sci. 129(4):665-72. doi: 10.1242/jcs.182469

BTW, whatever happened with Turing’s magic “one size fit all” plain vanilla diffusion? Sometimes reductionist thinking doesn't work in biology. Plain diffusion is fine for some color patterning and stuff like that, but not for many cases where things get tough. Additional factors are required too. OK? Complex complexityDionisio_{July 5, 2017
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Regulation of propagation is fundamental to the formation of a Wnt8a morphogenetic gradient. However, how Wnt proteins are distributed to form this gradient and function over tens of micrometers is still unclear.
Role of cytonemes in Wnt transport. Stanganello E, Scholpp S J Cell Sci. 129(4):665-72. doi: 10.1242/jcs.182469

Complex complexityDionisio_{July 5, 2017
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During embryogenesis, all multicellular organisms face the same fundamental challenge: the development of a complex structure originating from a single cell. One of the first steps of development is the establishment of the embryonic body plan. [...] the extracellular transport mechanism of this morphogen from the signal-releasing cell to the recipient cell is still debated. [...] recent evidences of a cytoneme-mediated transport in development and in the stem cell niche. This unexpected trafficking mode raises numerous questions with regard to morphogenetic gradient formation within a growing tissue, which we will address in the concluding section of the article.
Role of cytonemes in Wnt transport. Stanganello E, Scholpp S J Cell Sci. 129(4):665-72. doi: 10.1242/jcs.182469

Did somebody say "plan"? Did somebody say "unexpected"? Why? What else did they expect? BTW, whatever happened with Turing's magic "one size fit all" diffusion? Complex complexityDionisio_{July 5, 2017
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Wnt signaling regulates a broad variety of processes during embryonic development and disease. A hallmark of the Wnt signaling pathway is the formation of concentration gradients by Wnt proteins across responsive tissues, which determines cell fate in invertebrates and vertebrates. To fulfill its paracrine function, trafficking of the Wnt morphogen from an origin cell to a recipient cell must be tightly regulated. A variety of models have been proposed to explain the extracellular transport of these lipid-modified signaling proteins in the aqueous extracellular space; however, there is still considerable debate with regard to which mechanisms allow the precise distribution of ligand in order to generate a morphogenetic gradient within growing tissue.
Role of cytonemes in Wnt transport. Stanganello E, Scholpp S J Cell Sci. 129(4):665-72. doi: 10.1242/jcs.182469

A couple of years ago a Canadian professor affirmed that he knew exactly how morphogen gradients form. Or at least that's what he implicitly stated when he responded to a dishonest question that contained the tricky word "exactly" which obviously he could not notice because it was not bold text. :) Complex complexityDionisio_{July 5, 2017
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While studies of stem cells have revealed a great deal about maintenance and propagation, the origin of most adult stem cell populations remains an open question. [...] local trapping of a broadly secreted signal may be a mechanism that is widely employed in a variety of embryological contexts. [...] our findings compel investigation into potential embryonic origins for other adult stem cells.
Bending gradients: How the intestinal stem cell gets its home Amy E. Shyer, Tyler R. Huycke, ChangHee Lee, L. Mahadevan, and Clifford J. Tabin Cell. 161(3): 569–580. doi: 10.1016/j.cell.2015.03.041

Note that this paper was first referenced @813, but only the summary was quoted. Complex complexityDionisio_{July 5, 2017
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Surprisingly, we found that BMP activity had no effect on the total number of cells in the mesentery, despite dramatic changes in overall tissue volume. It is unclear whether such mechanisms are at work in the developing gut. An interesting, albeit at this point speculative, possibility is that the signals controlling growth of the mesentery are themselves under control of physical forces, creating a feedback loop. [...] loop morphology depends not only on differential growth, but on geometry and stiffness of the tube and mesentery as well.
BMP signaling controls buckling forces to modulate looping morphogenesis of the gut Nandan L. Nerurkar, L. Mahadevan, and Clifford J. Tabin doi: 10.1073/pnas.1700307114 PNAS vol. 114 no. 9 2277-2282

Did somebody say "Surprisingly"? Complex complexityDionisio_{July 5, 2017
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Differential growth represents one of the core physical mechanisms driving morphogenesis throughout the vertebrate embryo [...] Looping maximizes the absorptive capacity of the gut by allowing intestinal length to extend well beyond the linear length of the organism, while maintaining an ordered configuration in the body cavity. [...] regulation of tissue-scale physical forces can be traced to signaling pathways during vertebrate development.
BMP signaling controls buckling forces to modulate looping morphogenesis of the gut Nandan L. Nerurkar, L. Mahadevan, and Clifford J. Tabin doi: 10.1073/pnas.1700307114 PNAS vol. 114 no. 9 2277-2282

Complex complexityDionisio_{July 5, 2017
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Looping of the initially straight embryonic gut tube is an essential aspect of intestinal morphogenesis, permitting proper placement of the lengthy small intestine within the confines of the body cavity. Although the physics of this process has been studied, the underlying biology has not.
BMP signaling controls buckling forces to modulate looping morphogenesis of the gut Nandan L. Nerurkar, L. Mahadevan, and Clifford J. Tabin doi: 10.1073/pnas.1700307114 PNAS vol. 114 no. 9 2277-2282

Complex complexityDionisio_{July 5, 2017
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Growth regulation is needed to form organs of correct size and proportion, but the mechanisms that define organ and organism size remain poorly understood [...] Hippo signaling is activated within faster growing clones as a consequence of cellular compression, rather than through biochemical pathways dependent upon the various genotypes analyzed. [...] when compression-induced growth suppression is bypassed by genetic manipulations that suppress mechanical feedback, higher cell proliferation is observed in the center of the wing disc.
Differential growth triggers mechanical feedback that elevates Hippo signaling. Pan Y, Heemskerk I, Ibar C, Shraiman BI, Irvine KD Proc Natl Acad Sci U S A. 113(45): E6974–E6983. doi: 10.1073/pnas.1615012113 PMCID: PMC5111668 PNAS Plus Developmental Biology, Physics

Complex complexityDionisio_{July 5, 2017
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To form organs of correct size and proportion, growth must be tightly controlled. Our results support and extend a theoretical model, termed “mechanical feedback,” that described the relationship between growth rates and tissue mechanics.
Differential growth triggers mechanical feedback that elevates Hippo signaling. Pan Y, Heemskerk I, Ibar C, Shraiman BI, Irvine KD Proc Natl Acad Sci U S A. 113(45): E6974–E6983. doi: 10.1073/pnas.1615012113 PMCID: PMC5111668 PNAS Plus Developmental Biology, Physics

Complex complexityDionisio_{July 5, 2017
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The striking parallelisms in the molecules and mechanisms underlying limb development in vertebrates and invertebrates have contributed to the proposal that an ancient patterning system is being recurrently used to generate body wall outgrowths. Whether the conserved JAK/STAT pathway plays a developmental role also in the specification or growth of vertebrate limbs by regulating morphogen production or activity is a tempting question that remains to be elucidated.
JAK/STAT controls organ size and fate specification by regulating morphogen production and signalling. Recasens-Alvarez C, Ferreira A, Milán M Nat Commun. 8:13815. doi: 10.1038/ncomms13815.

Complex complexityDionisio_{July 4, 2017
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Morphogens of the Wnt/Wg, Shh/Hh and BMP/Dpp families regulate tissue growth and pattern formation in vertebrate and invertebrate limbs. Early in wing development, two distinct mechanisms ensure the spatial segregation of two alternative cell fates. Whether this apoptosis plays a biological role and relies on En activity requires further study.
JAK/STAT controls organ size and fate specification by regulating morphogen production and signalling. Recasens-Alvarez C, Ferreira A, Milán M Nat Commun. 8:13815. doi: 10.1038/ncomms13815.

Complex complexityDionisio_{July 4, 2017
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A complex set of interactions between morphogens and their corresponding signalling pathways contributes to patterning and organizing limb growth along the dorsal–ventral, anterior–posterior and proximal–distal axes.
JAK/STAT controls organ size and fate specification by regulating morphogen production and signalling. Recasens-Alvarez C, Ferreira A, Milán M Nat Commun. 8:13815. doi: 10.1038/ncomms13815.

Complex complexityDionisio_{July 4, 2017
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Despite the great differences in size and shape across the animal phyla, the body plan of most organisms is built up by a limited and conserved number of developmental toolkit genes that follow the same principles of animal design.
JAK/STAT controls organ size and fate specification by regulating morphogen production and signalling. Recasens-Alvarez C, Ferreira A, Milán M Nat Commun. 8:13815. doi: 10.1038/ncomms13815.

Did somebody say "design"? :) Complex complexityDionisio_{July 4, 2017
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A stable pool of morphogen-producing cells is critical for the development of any organ or tissue. [...] JAK/STAT signalling in the Drosophila wing promotes the cycling and survival of Hedgehog-producing cells, thereby allowing the stable localization of the nearby BMP/Dpp-organizing centre in the developing wing appendage.
JAK/STAT controls organ size and fate specification by regulating morphogen production and signalling. Recasens-Alvarez C, Ferreira A, Milán M Nat Commun. 8:13815. doi: 10.1038/ncomms13815.

Complex complexityDionisio_{July 4, 2017
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[...] sal promotes ban expression in the wing disc in a non-regional specific manner, unlike the manner of omb. [...] sal may mediate partial functions of Dpp in growth control. Other possibility is that sal may mediate the roles of other upstream factors such as Lines41, Wingless42, and Ubx in Drosophila43 as well as Tribolium44.
spalt is functionally conserved in Locusta and Drosophila to promote wing growth. Wang D, Li J, Liu S, Zhou H, Zhang L, Shi W, Shen J Sci Rep. 2017 Mar 16;7:44393. doi: 10.1038/srep44393.

Complex complexityDionisio_{July 4, 2017
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[...] little is known about the molecular mechanism of how the Locusta wing develops into such delicate structure. The pattern formation is delicately regulated by organizers located in the anterior/posterior (A/P) and dorsal/ventral (D/V) boundaries which secrete signal molecules including the long-range morphogens Decapentaplegic (Dpp) and Wingless (Wg)11,12, and short-range morphogen Hedgehog (Hh)13. These morphogens form gradients to regulate the expression of their target genes and control almost all aspects of wing development12.
spalt is functionally conserved in Locusta and Drosophila to promote wing growth. Wang D, Li J, Liu S, Zhou H, Zhang L, Shi W, Shen J Sci Rep. 2017 Mar 16;7:44393. doi: 10.1038/srep44393.

Complex complexity [this paper was first referenced @3471]Dionisio_{July 4, 2017
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The Hedgehog pathway is a pivotal morphogenic driver during embryonic development and a key regulator of adult stem cell self-renewal. The identification of critical soluble factors (such as Hedgehog) and the relevant cell-cell interactions that dictate the behaviour and fate of resident vascular stem cell niches should lead to the development of diagnostic markers and new therapeutic targets for intervention in degenerative/regenerative disease of the arterial wall.
Hedgehog and Resident Vascular Stem Cell Fate Ciaran J. Mooney, 1 Roya Hakimjavadi, 1 Emma Fitzpatrick, 1 Eimear Kennedy, 1 Dermot Walls, 2 David Morrow, 3 Eileen M. Redmond, 3 and Paul A. Cahill Stem Cells Int. 468428. doi: 10.1155/2015/468428

Complex complexityDionisio_{July 4, 2017
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This paper was referenced @1408 & @1124
Robust and precise morphogen-mediated patterning: trade-offs, constraints and mechanisms

Dionisio_{July 4, 2017
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Locusta has strong fly wings to ensure its long distance migration, but the molecular mechanism that regulates the Locusta wing development is poorly understood.
Sci Rep. 2017 Mar 16;7:44393. doi: 10.1038/srep44393. spalt is functionally conserved in Locusta and Drosophila to promote wing growth. Wang D1, Li J1, Liu S1, Zhou H1, Zhang L1, Shi W1, Shen J

Complex complexityDionisio_{July 3, 2017
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