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The “beautiful mechanism” by which an egg becomes an embryo

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From Phys.org:

The transition from an egg to a developing embryo is one of life’s most remarkable transformations. Yet little is known about it. Now Whitehead Institute researchers have deciphered how one aspect—control of the all-important translation of messenger RNAs (mRNAs) into proteins—switches as the egg becomes an embryo. That shift is controlled by a beautiful mechanism, which is triggered at a precise moment in development and automatically shuts itself off after a narrow window of 20 to 90 minutes.

As an egg develops, it stockpiles mRNAs from the mother because it will not have time to create new mRNAs during the rapid development of a very early embryo. When fertilized the egg becomes an embryo, the stashed maternal mRNAs are pressed into service for a brief window before the embryo starts transcribing its own mRNAs. This change occurs very early; in humans, only two to four cell divisions occur before this transition is executed. Whitehead Member Terry Orr-Weaver studies the control of translation of maternal mRNAs in the model organism Drosophila, or the fruit fly, because its developmental strategy offers experimental advantages. More.

A reader writes to note that the “beautiful mechanism” is described as a

negative feedback loop,” with the same function as those designed in engineering control systems: Furthermore, the activity of PNG kinase leads to the destruction of GNU, and this feedback loop limits this kinase’s activity to the narrow window of time in which it is needed.

“Active PNG leads to decreased GNU protein levels. This makes a negative feedback to shut down PNG kinase activity, thereby ensuring PNG kinase activity is constrained to the short developmental window of the oocyte-to-embryo transition

Another reader who forwarded this item points out that the authors let in the “d” word (and I don’t mean “Darwin”…. ):

The design of this transition could tell scientists more about how human cells work and embryos develop. For example, the switch could be a model for how cells massively and globally change mRNA translation. Also, similar kinase activity during early development has been noted in worms, which may mean that a comparable approach is used in other organisms, including humans.

Well, if the researchers’ careers take a beating for mentioning design, they will need to join the Free the Universities movement. After a while language Stalinism starts t collapse from its own uncommunicativeness and one must peak clearly again.

See also: Cells communicate to navigate a crowded embryo

Comments
[...] the regulation of asymmetric and symmetric cell divisions plays a fundamental role in the generation of cell diversity in the developing cortex [...] By orienting the angle of mitotic cleavage, cleavage furrows could segregate determinants symmetrically or asymmetrically to produce equal or unequal daughter cells [...]
Afadin controls cell polarization and mitotic spindle orientation in developing cortical radial glia Jennifer Rakotomamonjy, Molly Brunner, Christoph Jüschke, Keling Zang, Eric J. Huang, Louis F. Reichardt, Anjen Chen Neural Dev (2017) 12: 7. https://doi.org/10.1186/s13064-017-0085-2
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Afadin plays an essential role in regulating apical-basal polarity and adherens junction integrity of radial glial cells, and suggest that epithelial architecture plays an important role in radial glial identity by regulating mitotic orientation and preventing premature exit from the neurogenic niche.
Afadin controls cell polarization and mitotic spindle orientation in developing cortical radial glia Jennifer Rakotomamonjy, Molly Brunner, Christoph Jüschke, Keling Zang, Eric J. Huang, Louis F. Reichardt, Anjen Chen Neural Dev (2017) 12: 7. https://doi.org/10.1186/s13064-017-0085-2
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[...] clonally related chondrocytes become arranged in either single or multi-columns along the axis of tissue elongation. These columnar morphologies are generated through two types of cell behaviors: cell pivoting resulting in single columns or cell intercalation resulting in complex columns. The PCP pathway coordinates cell pivoting following mediolateral division. In this way, chondrocytes increase their cell numbers while concomitantly undergoing stereotypical arrangements that result in tissue elongation. [...] this highlights the importance of PCP signaling in shaping tissues via regulating polarized cell behaviors.
Planar cell polarity signaling coordinates oriented cell division and cell rearrangement in clonally expanding growth plate cartilage Yuwei Li, Ang Li, Jason Junge, Marianne Bronner eLife 2017;6:e23279 doi: 10.7554/eLife.23279
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A central question in modern biology is how cells build a complex tissue within a four dimensional (xyz and t) context. This is particularly true in developing embryos, in which cells undergo intricate behaviors including proliferation, migration and differentiation, while interacting with similar as well as distinct cell types. Two fundamental cellular processes, oriented cell divisions and cell rearrangements, play important roles during tissue growth [...]
Planar cell polarity signaling coordinates oriented cell division and cell rearrangement in clonally expanding growth plate cartilage Yuwei Li, Ang Li, Jason Junge, Marianne Bronner eLife 2017;6:e23279 doi: 10.7554/eLife.23279
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The actomyosin ring generates force to ingress the cytokinetic cleavage furrow in animal cells, yet its filament organization and the mechanism of contractility is not well understood. [...] cleavage furrow ingression initiates by contraction of an equatorial actin network with randomly oriented filaments. The network subsequently gradually reoriented actin filaments along the cell equator. [...] during cytokinesis progression, mechanical tension increased substantially along the direction of the cell equator, while the network contracted laterally along the pole-to-pole axis without a detectable increase in tension. [...] an asymmetric increase in cortical tension promotes filament reorientation along the cytokinetic cleavage furrow, which might have implications for diverse other biological processes involving actomyosin rings.
Cytokinesis in vertebrate cells initiates by contraction of an equatorial actomyosin network composed of randomly oriented filaments Felix Spira, Sara Cuylen-Haering, Shalin Mehta, Matthias Samwer, Anne Reversat, Amitabh Verma, Rudolf Oldenbourg, Michael Sixt, Daniel W Gerlich eLife 2017;6:e30867 doi: 10.7554/eLife.30867
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Both oriented cell divisions and cell rearrangements are critical for proper embryogenesis and organogenesis. However, little is known about how these two cellular events are integrated. Our work provides new insights into the mechanisms generating appropriate tissue architecture of limb skeleton.
Planar cell polarity signaling coordinates oriented cell division and cell rearrangement in clonally expanding growth plate cartilage Yuwei Li, Ang Li, Jason Junge, Marianne Bronner eLife 2017;6:e23279 doi: 10.7554/eLife.23279
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Stem cells self-renew but also give rise to daughter cells that are committed to lineage-specific differentiation. To achieve this remarkable task, they can undergo an intrinsically asymmetric cell division whereby they segregate cell fate determinants into only one of the two daughter cells. Alternatively, they can orient their division plane so that only one of the two daughter cells maintains contact with the niche and stem cell identity. Although the molecules involved are highly conserved in vertebrates, the way they act is tissue specific and sometimes very different from invertebrates.
Mechanisms of Asymmetric Stem Cell Division Juergen A. Knoblich DOI: http://dx.doi.org/10.1016/j.cell.2008.02.007 Cell Volume 132, Issue 4, p583–597
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Gut microbes can shape responses to cancer immunotherapy Studies find that species diversity and antibiotics influence cutting-edge treatments. http://www.nature.com/news/gut-microbes-can-shape-responses-to-cancer-immunotherapy-1.22938
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Critical steps in forming the vertebrate limb include the positioning of digits and the positioning of joints within each digit. Recent studies have proposed that the iterative series of digits is established by a Turing-like mechanism generating stripes of chondrogenic domains. However, re-examination of available data suggest that digits are actually patterned as evenly spaced spots, not stripes, which then elongate into rod-shaped digit rays by incorporating new cells at their tips. Moreover, extension of the digit rays and the patterning of the joints occur simultaneously at the distal tip, implying that an integrated model is required to fully understand these processes.
On the Formation of Digits and Joints during Limb Development Tom W. Hiscock, Patrick Tschopp, Clifford J. Tabin Volume 41, Issue 5, p459–465 Developmental Cell DOI: http://dx.doi.org/10.1016/j.devcel.2017.04.021
A Turing-like mechanism doesn't seem to explain the observed facts? an integrated model is required to fully understand these processes? Complex functionally specified informational complexityDionisio
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Vertebrate limb development relies on the activity of signaling centers that promote growth and control patterning along three orthogonal axes of the limb bud. The apical ectodermal ridge, at the distal rim of the limb bud ectoderm, produces WNT and FGF signals, which promote limb bud growth and progressive distalization. The zone of polarizing activity, a discrete postero-distal mesenchymal domain, produces SHH, which stimulates growth and organizes patterning along the antero-posterior axis. The dorsal and ventral ectoderms produce, respectively, WNT7A and BMPs, which induce dorso-ventral limb fates. Interestingly, these signaling centers and the mechanisms they instruct interact with each other to coordinate events along the three axes.
Coordination of limb development by crosstalk among axial patterning pathways Irene Delgado, Miguel Torres ScienceDirect / Developmental Biology Volume 429, Issue 2, Pages 382-386 https://doi.org/10.1016/j.ydbio.2017.03.006
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[...] the mechanism by which Shh patterns the limb, how it acts to instruct digit 'identity', nevertheless remains an enigma. This review focuses on what has been learned about Shh function in the limb and the outstanding puzzles that remain to be solved.
John Saunders' ZPA, Sonic hedgehog and digit identity - How does it really all work? Zhu J1, Mackem S Dev Biol. 429(2):391-400. doi: 10.1016/j.ydbio.2017.02.001.
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[...] there is no single generic mechanism of SMAD2-mediated transcription, but rather it is gene specific and can occur in an acute or delayed fashion and can be activatory or repressive. The initial transcriptional profile is modulated at later time points as a result of both delayed SMAD2 binding, and subsequent binding of repressors to already occupied SBSs. Future work will aim to identify TFs and enzymes that collaborate with the SMADS to modulate the transcriptional response over time, allowing cells to correctly execute gene expression programs in response to TGF-? superfamily signaling.
Distinct modes of SMAD2 chromatin binding and remodeling shape the transcriptional response to NODAL/Activin signaling. Coda DM1, Gaarenstroom T1, East P2, Patel H2, Miller DS1, Lobley A2, Matthews N3, Stewart A2, Hill CS1 Elife.;6. pii: e22474. doi: 10.7554/eLife.22474.
Work in progress... stay tuned. Complex functionally specified informational complexityDionisio
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Patterning of tissues during embryonic development depends on the control of gene expression by extracellular signals. The signaling molecules involved frequently act as morphogens to impart positional information [...] [...] we know little about the sequence of events that occur from TF binding to the induction of dynamic programs of gene expression. We go on to define the sequence of events that occur from SMAD2 binding to transcriptional activation, and the mechanisms underlying them. Our work establishes new paradigms for signal-dependent transcriptional regulation.
Distinct modes of SMAD2 chromatin binding and remodeling shape the transcriptional response to NODAL/Activin signaling. Coda DM1, Gaarenstroom T1, East P2, Patel H2, Miller DS1, Lobley A2, Matthews N3, Stewart A2, Hill CS1 Elife.;6. pii: e22474. doi: 10.7554/eLife.22474.
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To allow a complex animal to develop from a small bundle of cells, the cells need to be able to communicate with each other to coordinate their activities. [...] it is not clear how the detection of these signals at the surface of the cell leads to changes in the activity of genes inside the nucleus. Two transforming growth factor beta signals called Activin and NODAL cause a transcription factor known as SMAD2 to move into the nucleus where it can alter gene activity. [...] future experiments will investigate which other proteins help SMAD2 to change gene activity at later times.
Distinct modes of SMAD2 chromatin binding and remodeling shape the transcriptional response to NODAL/Activin signaling. Coda DM1, Gaarenstroom T1, East P2, Patel H2, Miller DS1, Lobley A2, Matthews N3, Stewart A2, Hill CS1 Elife.;6. pii: e22474. doi: 10.7554/eLife.22474.
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NODAL/Activin signaling orchestrates key processes during embryonic development via SMAD2. How SMAD2 activates programs of gene expression that are modulated over time however, is not known. Thus SMAD2 binding does not linearly equate with transcriptional kinetics [...] [...] SMAD2 recruits multiple co-factors during sustained signaling to shape the downstream transcriptional program.
Distinct modes of SMAD2 chromatin binding and remodeling shape the transcriptional response to NODAL/Activin signaling. Coda DM1, Gaarenstroom T1, East P2, Patel H2, Miller DS1, Lobley A2, Matthews N3, Stewart A2, Hill CS1 Elife.;6. pii: e22474. doi: 10.7554/eLife.22474.
Did somebody say 'orchestrates'? Did somebody say 'programs'? Complex functionally specified informational complexityDionisio
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The factors that control HSPC fate decision remain unclear. [...] our data reveal what may be a novel function for TGF-? in HSC self-renewal activity as fate determinant to modulate HSC activity.
p190-B RhoGAP and intracellular cytokine signals balance hematopoietic stem and progenitor cell self-renewal and differentiation Ashwini Hinge,1 Juying Xu,1 Jose Javier,1 Eucabeth Mose,1 Sachin Kumar,1 Reuben Kapur,2 Edward F. Srour,2 Punam Malik,1 Bruce J. Aronow,3 and Marie-Dominique Filippi Nat Commun. 2017; 8: 14382. doi: 10.1038/ncomms14382
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Erythroid enucleation embodies many features of an asymmetric cell division[1–10] and results in the generation of two unique daughter cells: the pyrenocyte containing the condensed nucleus and the anucleated reticulocyte that will further mature into the erythrocyte found in the peripheral blood.
The Asymmetric Cell Division Regulators Par3, Scribble and Pins/Gpsm2 Are Not Essential for Erythroid Development or Enucleation. Wölwer CB1,2, Gödde N1,2, Pase LB1, Elsum IA1, Lim KY2, Sacirbegovic F3,4, Walkley CR5,6, Ellis S3,4, Ohno S7, Matsuzaki F8, Russell SM4,9,10, Humbert PO1,2,4,9,11. PLoS One. 12(1):e0170295. doi: 10.1371/journal.pone.0170295
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Erythroid enucleation is the process by which the future red blood cell disposes of its nucleus prior to entering the blood stream. This key event during red blood cell development has been likened to an asymmetric cell division (ACD), by which the enucleating erythroblast divides into two very different daughter cells of alternate molecular composition, a nucleated cell that will be removed by associated macrophages, and the reticulocyte that will mature to the definitive erythrocyte. Together our results put into question a role for cell polarity and asymmetric cell division in erythroid enucleation.
The Asymmetric Cell Division Regulators Par3, Scribble and Pins/Gpsm2 Are Not Essential for Erythroid Development or Enucleation. Wölwer CB1,2, Gödde N1,2, Pase LB1, Elsum IA1, Lim KY2, Sacirbegovic F3,4, Walkley CR5,6, Ellis S3,4, Ohno S7, Matsuzaki F8, Russell SM4,9,10, Humbert PO1,2,4,9,11. PLoS One. 12(1):e0170295. doi: 10.1371/journal.pone.0170295
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Transcription factors such as KLF1, along with epigenetic modifiers, play crucial roles in establishing the proper onset and progression of terminal differentiation events. [...] the orthochromatic erythroblast stage is a critical nodal point for many of the effects on enucleation.
Orchestration of late events in erythropoiesis by KLF1/EKLF. Gnanapragasam MN1, Bieker JJ. Curr Opin Hematol. 24(3):183-190. doi: 10.1097/MOH.0000000000000327
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Biogenesis of mammalian red blood cells requires nuclear expulsion by orthochromatic erythoblasts late in terminal differentiation (enucleation), but the mechanism is largely unexplained. This novel structure, the "enucleosome," may mediate common cytoskeletal mechanisms underlying erythroblast enucleation, notwithstanding the morphological heterogeneity of enucleation across species.
Tropomodulin 1 controls erythroblast enucleation via regulation of F-actin in the enucleosome. Nowak RB1, Papoin J2, Gokhin DS1, Casu C3, Rivella S3, Lipton JM2,4,5, Blanc L2,4,5, Fowler VM1 Blood. 130(9):1144-1155. doi: 10.1182/blood-2017-05-787051.
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[...] it may be insightful to reconsider morphogenetic gradient theory in terms of context-dependent profile features, such as minima with an inherent curvature, instead of absolute thresholds only.
Auxin minimum triggers the developmental switch from cell division to cell differentiation in the Arabidopsis root. Di Mambro R1, De Ruvo M1,2,3, Pacifici E1, Salvi E1, Sozzani R4, Benfey PN5,6, Busch W7, Novak O8, Ljung K8, Di Paola L2, Marée AFM3, Costantino P1, Grieneisen VA9, Sabatini S10,11. Proc Natl Acad Sci U S A. 114(36):E7641-E7649. doi: 10.1073/pnas.1705833114. http://www.pnas.org/content/114/36/E7641.full
Did somebody say "reconsider morphogenetic gradient theory" in 2017? Didn't a distinguished biochemistry professor claim two years ago, here in this website, that all is known about morphogen gradient formation? Why reconsider it now? Complex functionally specified informational complexityDionisio
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Future challenge will be to understand how the position of the auxin minimum correlates with the programmed cell death of the LRC and how these two inputs are coordinated to control the dynamic of root growth and the entire root system organization.
Auxin minimum triggers the developmental switch from cell division to cell differentiation in the Arabidopsis root. Di Mambro R1, De Ruvo M1,2,3, Pacifici E1, Salvi E1, Sozzani R4, Benfey PN5,6, Busch W7, Novak O8, Ljung K8, Di Paola L2, Marée AFM3, Costantino P1, Grieneisen VA9, Sabatini S10,11. Proc Natl Acad Sci U S A. 114(36):E7641-E7649. doi: 10.1073/pnas.1705833114. http://www.pnas.org/content/114/36/E7641.full
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It should be pointed out that the consistent correspondence between cytokinin-driven auxin minimum formation and root zonation reveals that auxin patterning guides the localization and stabilization of the TZ in a self-organizing manner where cytokinin may operate along with other inputs [...]
Auxin minimum triggers the developmental switch from cell division to cell differentiation in the Arabidopsis root. Di Mambro R1, De Ruvo M1,2,3, Pacifici E1, Salvi E1, Sozzani R4, Benfey PN5,6, Busch W7, Novak O8, Ljung K8, Di Paola L2, Marée AFM3, Costantino P1, Grieneisen VA9, Sabatini S10,11. Proc Natl Acad Sci U S A. 114(36):E7641-E7649. doi: 10.1073/pnas.1705833114. http://www.pnas.org/content/114/36/E7641.full
Do they mean that this is not the end of the story? Complex functionally specified informational complexityDionisio
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The peculiar feature of this auxin minimum consists in having the lowest auxin level (dip) within each tissue aligned in a cell row. This alignment of dips ensures the coordinated activity of the cells where the dip occurs, so that these cells will switch together to the differentiation program thus preserving the root structure and zonation.
Auxin minimum triggers the developmental switch from cell division to cell differentiation in the Arabidopsis root. Di Mambro R1, De Ruvo M1,2,3, Pacifici E1, Salvi E1, Sozzani R4, Benfey PN5,6, Busch W7, Novak O8, Ljung K8, Di Paola L2, Marée AFM3, Costantino P1, Grieneisen VA9, Sabatini S10,11. Proc Natl Acad Sci U S A. 114(36):E7641-E7649. doi: 10.1073/pnas.1705833114. http://www.pnas.org/content/114/36/E7641.full
Did somebody say 'coordinated'? Did somebody say 'program'? Complex functionally specified informational complexityDionisio
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Understanding how boundaries are maintained during organ growth is a fundamental question in developmental biology. [...] auxin minimum acts as a positional signal that triggers the developmental switch from cell division to cell differentiation.
Auxin minimum triggers the developmental switch from cell division to cell differentiation in the Arabidopsis root. Di Mambro R1, De Ruvo M1,2,3, Pacifici E1, Salvi E1, Sozzani R4, Benfey PN5,6, Busch W7, Novak O8, Ljung K8, Di Paola L2, Marée AFM3, Costantino P1, Grieneisen VA9, Sabatini S10,11. Proc Natl Acad Sci U S A. 114(36):E7641-E7649. doi: 10.1073/pnas.1705833114. http://www.pnas.org/content/114/36/E7641.full
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The maintenance of boundaries between neighboring groups of distinct cell types is vital during development of multicellular organisms, as groups of cells with distinct functions must be kept physically separated to guarantee correct control of organ and body growth and function. [...] a well-defined and tightly controlled minimum of the hormone auxin acts as a signal to establish the position of the transition zone by controlling the developmental switch from cell division to cell differentiation. [...] another hormone, cytokinin, controls and positions this auxin minimum, thus regulating root size.
Auxin minimum triggers the developmental switch from cell division to cell differentiation in the Arabidopsis root. Di Mambro R1, De Ruvo M1,2,3, Pacifici E1, Salvi E1, Sozzani R4, Benfey PN5,6, Busch W7, Novak O8, Ljung K8, Di Paola L2, Marée AFM3, Costantino P1, Grieneisen VA9, Sabatini S10,11. Proc Natl Acad Sci U S A. 114(36):E7641-E7649. doi: 10.1073/pnas.1705833114. http://www.pnas.org/content/114/36/E7641.full
How is citokinin controlled? Complex functionally specified informational complexityDionisio
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[...] boundary formation is dependent on cytokinin's control on auxin polar transport and degradation. The regulation of both processes shapes the auxin profile in a well-defined auxin minimum. This auxin minimum positions the boundary between dividing and differentiating cells, acting as a trigger for this developmental transition, thus controlling meristem size.
Auxin minimum triggers the developmental switch from cell division to cell differentiation in the Arabidopsis root. Di Mambro R1, De Ruvo M1,2,3, Pacifici E1, Salvi E1, Sozzani R4, Benfey PN5,6, Busch W7, Novak O8, Ljung K8, Di Paola L2, Marée AFM3, Costantino P1, Grieneisen VA9, Sabatini S10,11. Proc Natl Acad Sci U S A. 114(36):E7641-E7649. doi: 10.1073/pnas.1705833114. http://www.pnas.org/content/114/36/E7641.full
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In multicellular organisms, a stringent control of the transition between cell division and differentiation is crucial for correct tissue and organ development. In the Arabidopsis root, the boundary between dividing and differentiating cells is positioned by the antagonistic interaction of the hormones auxin and cytokinin. Cytokinin affects polar auxin transport, but how this impacts the positional information required to establish this tissue boundary, is still unknown.
Auxin minimum triggers the developmental switch from cell division to cell differentiation in the Arabidopsis root. Di Mambro R1, De Ruvo M1,2,3, Pacifici E1, Salvi E1, Sozzani R4, Benfey PN5,6, Busch W7, Novak O8, Ljung K8, Di Paola L2, Marée AFM3, Costantino P1, Grieneisen VA9, Sabatini S10,11. Proc Natl Acad Sci U S A. 114(36):E7641-E7649. doi: 10.1073/pnas.1705833114. http://www.pnas.org/content/114/36/E7641.full
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Transcription of a 5’ extended mRNA isoform directs dynamic chromatin changes and interference of a downstream promoter Minghao Chia, Amy Tresenrider, Jingxun Chen, Gianpiero Spedale, Victoria Jorgensen, Elçin Ünal, Folkert Jacobus van Werven DOI: 10.7554/eLife.27420 eLife
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The bouquet arrangement is highly conserved among eukaryotes [6, 7], and how it is formed and what functions it has are important questions in the field of meiosis. [...] conservation of the regulatory mechanisms is currently unclear [...] [...] our findings may also be relevant for understanding the chromosome positioning-dependent mechanisms that regulate development and differentiation of other organisms.
A Taz1- and Microtubule-Dependent Regulatory Relationship between Telomere and Centromere Positions in Bouquet Formation Secures Proper Meiotic Divisions. Katsumata K1, Hirayasu A1, Miyoshi J2, Nishi E1, Ichikawa K1, Tateho K1, Wakuda A2, Matsuhara H3, Yamamoto A PLoS Genet. 12(9):e1006304. doi: 10.1371/journal.pgen.1006304.
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