Mystery at the heart of life

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December 21, 2014

Cell biology, Intelligent Design, News

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Cell biology
Intelligent Design
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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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Regulation of NDR1 activity by PLK1 ensures proper spindle orientation in meiosis Maomao Yan, Lingluo Chu, Bo Qin, Zhikai Wang, Xing Liu, Changjiang Jin, Guanglan Zhang, Marta Gomez, Alexander Hergovich, Zhengjun Chen, Ping He, Xinjiao Gao & Xuebiao Yao Scientific Reports 5, Article number: 10449 doi:10.1038/srep10449 http://www.nature.com/srep/2015/150609/srep10449/full/srep10449.html Accurate development of multicellular organism requires well-orchestrated symmetric and asymmetric cell division. [...] the mechanisms underlying PLK1 signaling in spindle positioning and orientation have not been fully illustrated. Future work will be required to define the molecular basis underlying the aforementioned PLK1-elicited NDR1-Mob2 interaction and delineate the respective role of each of three phosphorylation sites in mediating NDR1-binder switch. [...] the molecular nature of PLK1 substrates involved in spindle positioning remains to be identified. Future studies will also address whether and how NDR1 regulates NuMA-LGN/G?i interaction at the cell cortex.
Work in progress... stay tuned.Dionisio_{July 14, 2015
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Engineers’ Muse: The Design of Biochemical Systems http://www.reasons.org/articles/engineers-muse-the-design-of-biochemical-systemsDionisio_{July 14, 2015
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Characterization of Ring-Like F-Actin Structure as a Mechanical Partner for Spindle Positioning in Mitosis Huan Lu , Qun Zhao , Hao Jiang, Tongge Zhu, mPeng Xia, William Seffens, Felix Aikhionbare, Dongmei Wang, Zhen Dou, Xuebiao Yao http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0102547 •DOI: 10.1371/journal.pone.0102547 Proper spindle positioning and orientation are essential for accurate mitosis which requires dynamic interactions between microtubule and actin filament (F-actin). Although mounting evidence demonstrates the role of F-actin in cortical cytoskeleton dynamics, it remains elusive as to the structure and function of F-actin-based networks in spindle geometry. Our computational modeling of spindle position process suggests a possible mechanism by which the ring-like F-actin structure can regulate astral microtubule dynamics and thus mitotic spindle orientation. These findings reveal a previously unrecognized but important link between mitotic spindle and ring-like F-actin network in accurate mitosis [...] Comparing the biochemical mechanism of mitotic spindle, the biophysical mechanism, especially a mechanical force chain stretching across the mitotic cell, remains elusive. [...] it remains elusive on how the cytoplasmic force rather than the cortical affects the spindle. We have also raised questions on the formation, the structural property and the physical meanings of the ring-like F-actin structure. The 3D projection has also suggested possible links between the ring-like F-actin structure and spindle positioning. Further experiments are needed to clarify the molecular mechanism.
Some outstanding questions answered. New questions raised.Dionisio_{July 14, 2015
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Shaping up to divide: Coordinating actin and microtubule cytoskeletal remodelling during meiosis Oscar M. Lancaster, Buzz Baum doi:10.1016/j.semcdb.2014.02.015 Cell division requires the wholesale reorganization of cell architecture. At the same time as the microtubule network is remodelled to generate a bipolar spindle, animal cells entering mitosis replace their interphase actin cytoskeleton with a contractile mitotic actomyosin cortex that is tightly coupled to the plasma membrane – driving mitotic cell rounding. Here, we consider how these two processes are coordinated to couple chromosome segregation and cell division. In doing so we explore the relative roles of cell shape and the actin cortex in spindle morphogenesis, orientation and positioning. • This review explores the roles of cell shape and the actin cortex in spindle morphogenesis and positioning. • The actin cytoskeleton contributes to spindle morphogenesis through its protective effect on mitotic cell shape. • The actin cytoskeleton contributes to spindle positioning as an intermediary between the spindle and a cell's external environment. http://www.sciencedirect.com/science/article/pii/S1084952114000275
Fascinating choreography - another area open to exploration. Work in progress... stay tuned.Dionisio_{July 14, 2015
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Force and the spindle: Mechanical cues in mitotic spindle orientation Alexander Nestor-Bergmann1, Georgina Goddard1, Sarah Woolner doi:10.1016/j.semcdb.2014.07.008 http://www.sciencedirect.com/science/article/pii/S1084952114002195 this field is still in its infancy and there is much left to understand. our knowledge of the molecular mechanisms required to orient the spindle to external force is very sketchy. it will be of great interest to determine what sits upstream of actin organization in the transmission of external force to the spindle We also still need to unravel the contribution of cell shape from a more direct mechanism linking force to the spindle it is likely that the orientation of the mitotic spindle to mechanical cues is a widely used mechanism for coordinating cell division across complex tissues but, as yet, this has only been studied in the context of tissue morphogenesis and thus our understanding is very limited. It is tempting to speculate that linking force with spindle orientation could be a crucial mechanism in other tissue contexts where cell division is combined with a changing mechanical tissue environment It remains to be seen how mechanical forces might influence mitotic spindle orientation in these and other tissue contexts.
A few questions remain unanswered. Work in progress... stay tuned.Dionisio_{July 13, 2015
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One immediate challenge is to extend this high-resolution circuit analysis toward different visual behaviors, like color vision. Furthermore, important challenges remain. For instance, the complex problem of how correct synaptic connections between identified circuit elements are established, maintained, and regulated remains unsolved. Another major challenge lies in putting together the pieces of the puzzle by linking the developmental specification of cell types to the connectome as well as their functional role in the behaving animal. [...] whether Brn3b is crucial for the specification of these cells is unknown. http://genesdev.cshlp.org/content/28/23/2565.full So many pieces, one puzzle: cell type specification and visual circuitry in flies and mice Mathias F. Wernet1,2,3, Andrew D. Huberman4,5 and Claude Desplan2 doi: 10.1101/gad.248245.114 Genes & Dev. 28: 2565-2584 O
One challenge after another... URotURDionisio_{July 13, 2015
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Two transcription factors, Pou4f2 and Isl1, are sufficient to specify the retinal ganglion cell fate Fuguo Wua,b,c, Tadeusz J. Kaczynskia,b,c,d, Santhosh Sethuramanujamd,e, Renzhong Lia,b,c, Varsha Jaind,e, Malcolm Slaughterc,d,e, and Xiuqian Mua,b,c,d,f,1 doi: 10.1073/pnas.1421535112 PNAS 2015 vol. 112 no. 13 E1559-E1568 http://www.pnas.org/content/112/13/E1559.abstract [...] the mechanisms by which a retinal progenitor cell decides to adopt a particular cell type remain unclear. [...] the genetic and molecular basis for the specification of the RGC fate, a key step in RGC development, remains unclear.
A few questions remain unanswered. Work in progress... stay tuned.Dionisio_{July 13, 2015
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Connecting the Retina to the Brain Lynda Erskine1 Eloisa Herrera2 doi: 10.1177/1759091414562107 ASN Neuro vol. 6 no. 6 1759091414562107 http://asn.sagepub.com/content/6/6/1759091414562107.full The visual system is beautifully crafted to transmit information of the external world to visual processing and cognitive centers in the brain. For visual information to be relayed to the brain, a series of axon pathfinding events must take place to ensure that the axons of retinal ganglion cells, the only neuronal cell type in the retina that sends axons out of the retina, find their way out of the eye to connect with targets in the brain. [...] the wiring together of the developing visual system involves a complex interplay of genetic, molecular and activity based mechanisms. Visual function is critically dependent on the correct specification and generation of RGCs, and appropriate guidance of their axons to visual target regions in the brain. Guidance of RGC axons is not a simple process but requires integrated interactions between multiple coexpressed signals and modulatory factors, as well as regulation of intrinsic changes in growth cone responses and guidance cue expression. Once axons reach their targets, their task is far from complete, and molecular mechanisms act in concert with spontaneous activity to induce rearrangement and refinement of axon termini. Although our understanding of the mechanisms controlling visual system wiring has increased substantially over the past 10 to 20 years, much still remains to be established and will form a significant remaining challenge in the years to come.
Interesting paper. A few questions remain unanswered. Work in progress... stay tuned.Dionisio_{July 13, 2015
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Retinal waves regulate afferent terminal targeting in the early visual pathway Proc Natl Acad Sci U S A. 2015 Jun 2;112(22):E2957-66. doi: 10.1073/pnas.1506458112. Epub 2015 May 18. http://intl.pnas.org/content/112/22/E2957.abstract Our results provide a revision to the model of retinogeniculate development and to our general understanding of how neural activity guides the establishment of proper connectivity in the developing brain. Our results reveal a novel role for stage II retinal waves in regulating retinogeniculate afferent terminal targeting [...] These findings should contribute to answering questions regarding the role of neural activity in guiding the establishment of neural circuits.
Work in progress… stay tuned.Dionisio_{July 12, 2015
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#727 addendum #4
[...] the functional significance of the striking anatomical diversity that we describe, as well as the developmental mechanisms that generate it, remain subjects for future investigation.
Work in progress... stay tuned.Dionisio_{July 12, 2015
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#727 addendum #3
Nervous systems contain numerous and diverse cells displaying complex anatomical relationships. The specification and patterning of these cells must be generated by the execution of a much smaller set of instructions encoded in the genome. How many different genetic algorithms are needed? How precise are their outcomes? What types of rules do they follow? Answering such questions requires knowledge of the anatomy of neuronal processes for many different cell types, for numerous cells of the same type, and in multiple individuals. PNAS vol. 112 no. 22 > Aljoscha Nern, E2967–E2976, doi: 10.1073/pnas.1506763112 http://www.pnas.org/content/112/22/E2967
A few minor questions remain unanswered. Work in progress... stay tuned.Dionisio_{July 12, 2015
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#727 addendum #2
This unexpected diversity of coverage patterns provides multiple independent ways of integrating visual information across the retinotopic columns and implies the existence of multiple developmental mechanisms that generate these distinct patterns. PNAS vol. 112 no. 22 > Aljoscha Nern, E2967–E2976, doi: 10.1073/pnas.1506763112 http://www.pnas.org/content/112/22/E2967
Unexpected? why? what did they expect?Dionisio_{July 12, 2015
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#727 addendum #1
Similar to many brain regions, the medulla has a repetitive columnar structure that supports parallel information processing together with orthogonal layers of cell processes that enable communication between columns. PNAS vol. 112 no. 22 > Aljoscha Nern, E2967–E2976, doi: 10.1073/pnas.1506763112 http://www.pnas.org/content/112/22/E2967
Cool!Dionisio_{July 12, 2015
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Here's a potential confirmation of the prediction @726
Optimized tools for multicolor stochastic labeling reveal diverse stereotyped cell arrangements in the fly visual system Aljoscha Nern, Barret D. Pfeiffer, and Gerald M. Rubin PNAS vol. 112 no. 22 > Aljoscha Nern, E2967–E2976, doi: 10.1073/pnas.1506763112 http://www.pnas.org/content/112/22/E2967 Nervous systems contain vast numbers of neurons with diverse shapes and complex spatial relationships. We describe new genetic tools for the efficient visualization by light microscopy of individual neurons and their relative positions in Drosophila. The application of these methods to the visual system revealed an unexpected diversity of cell-type–specific arrangements of neuronal processes within a single brain region. This wide range of stereotyped cell arrangements provides distinct circuit elements for processing visual information and implies the existence of a surprisingly large number of genetic programs that produce these arrangements during development.
"unexpected diversity" ? surprisingly large number of genetic programs ? Why 'unexpected'? Why 'surprising'? Unending Revelation of the Ultimate RealityDionisio_{July 12, 2015
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Does this mean more discoveries ahead? Brainbow: New Resources and Emerging Biological Applications for Multicolor Genetic Labeling and Analysis http://www.genetics.org/content/199/2/293.abstract Versatile genetic paintbrushes: Brainbow technologies http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4384809/Dionisio_{July 12, 2015
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Spontaneous Neuronal Network Dynamics Reveal Circuit’s Functional Adaptations for Behavior Sebastián A. Romano, Thomas Pietri, Verónica Pérez-Schuster, Adrien Jouary, Mathieu Haudrechy, Germán Sumbre DOI: http://dx.doi.org/10.1016/j.neuron.2015.01.027 http://www.cell.com/neuron/fulltext/S0896-6273(15)00053-7
Dionisio_{July 12, 2015
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Donders is dead: cortical traveling waves and the limits of mental chronometry in cognitive neuroscience David M. Alexander, Chris Trengove and Cees van Leeuwen Cognitive Processing International Quarterly of Cognitive Science 2015 :662 DOI: 10.1007/s10339-015-0662-4 http://link.springer.com/article/10.1007/s10339-015-0662-4/fulltext.html Our results therefore bring into question Donders’ subtraction method, which is the basis for much of neuroscience and psychology experimentation. Future unraveling of these issues will be determined by the amount of signal explained by the different approaches, along with that signals’ explanatory power in behavior across settings, tasks, developmental stages, clinical groups and genetic diversity.
Dionisio_{July 11, 2015
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SUMOylation regulates ciliary localization of olfactory signaling proteins Jeremy C. McIntyre1, Ariell M. Joiner2, Lian Zhang1, Jorge Iñiguez-Lluhí2 and Jeffrey R. Martens1,* doi: 10.1242/?jcs.164673 2015 J Cell Sci 128, 1934-1945. http://jcs.biologists.org/content/128/10/1934 Although neuronal cilia, including those on olfactory sensory neurons (OSNs), are often delineated by localization of adenylyl cyclase 3 (AC3, also known as ADCY3), the mechanisms responsible for targeting integral membrane proteins are largely unknown. SUMOylation is necessary but not sufficient for ciliary trafficking of select constituents, further establishing the link between ciliary and nuclear import. Primary cilia are crucial cellular organelles that on many cells act as biological antennae detecting extracellular signals. An interesting phenomenon in the localization of proteins to cilia is that several mechanisms have been identified that are necessary but not sufficient for ciliary entry. [...] the diversity of mechanisms used for cilia localization varies, likely due to the membrane interactions of individual proteins and the cell type they are found in.
Work in progress... stay tuned.Dionisio_{July 9, 2015
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Expression and functions of long noncoding RNAs during human T helper cell differentiation Charles F. Spurlock III, John T. Tossberg, Yan Guo, Sarah P. Collier, Philip S. Crooke III & Thomas M. Aune Nature Communications 6, Article number: 6932 doi:10.1038/ncomms7932 http://www.nature.com/ncomms/2015/150423/ncomms7932/full/ncomms7932.html Long noncoding RNAs (lncRNAs) regulate an array of biological processes in cells and organ systems. Less is known about their expression and function in lymphocyte lineages.
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Constructing lncRNA functional similarity network based on lncRNA-disease associations and disease semantic similarity Xing Chen Chenggang Clarence Yan Cai Luo Wen Ji Yongdong Zhang Qionghai Dai Scientific Reports 5, Article number: 11338 doi:10.1038/srep11338 There are estimated 20,000 protein-coding genes in the human genome, which account for only approximately 1.5% of the whole genome. Therefore, more than 98% of the human genome does not encode protein sequences. Furthermore, plenty of evidences have demonstrated the critical regulative roles of noncoding RNAs (ncRNAs) in a broad range of fundamental and important biological processes, which challenge the traditional view that RNA is just transcriptional noise and intermediary between gene and protein Increasing evidence has indicated that plenty of lncRNAs play important roles in many critical biological processes. http://www.nature.com/srep/2015/150610/srep11338/full/srep11338.html
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The landscape of long noncoding RNAs in the human transcriptome Matthew K Iyer, Yashar S Niknafs, Rohit Malik, Udit Singhal, Anirban Sahu, Yasuyuki Hosono, Terrence R Barrette, John R Prensner, Joseph R Evans, Shuang Zhao, Anton Poliakov, Xuhong Cao, Saravana M Dhanasekaran, Yi-Mi Wu, Dan R Robinson, David G Beer, Felix Y Feng, Hariharan K Iyer & Arul M Chinnaiyan Nature Genetics 47, 199–208 (2015) doi:10.1038/ng.3192 Long noncoding RNAs (lncRNAs) are emerging as important regulators of tissue physiology and disease processes including cancer. http://www.nature.com/ng/journal/v47/n3/full/ng.3192.html
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Spatial reconstruction of single-cell gene expression data Rahul Satija, Jeffrey A Farrell, David Gennert, Alexander F Schier & Aviv Regev Nature Biotechnology 33, 495–502 (2015) doi:10.1038/nbt.3192 http://www.nature.com/nbt/journal/v33/n5/full/nbt.3192.html A major focus of developmental biology is understanding the origin and features of different cell types in complex tissues, including the gene expression modules that underlie specific cell types and states, the regulatory circuits that set up these expression programs, and the cell's molecular signals and interactions. In embryos at the late blastula stage, when cell fate is being decided on the basis of inputs from several morphogens whose gradients originate from different regions of the embryo, the spatial location of cells is paramount.
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Dynamics of a Volvox Embryo Turning Itself Inside Out Stephanie Höhn, Aurelia R. Honerkamp-Smith, Pierre A. Haas, Philipp Khuc Trong, and Raymond E. Goldstein Phys. Rev. Lett. 114, 178101 – 2015 http://dx.doi.org/10.1103/PhysRevLett.114.178101 http://journals.aps.org/prl/abstract/10.1103/PhysRevLett.114.178101 Deformations of cell sheets are ubiquitous in early animal development, often arising from a complex and poorly understood interplay of cell shape changes, division, and migration. Whether the observed cell shapes and the location and timing of their appearance result from a predefined program or are triggered by mechanical signals remains an open question.
A few questions remain unanswered. Work in progress... stay tuned.Dionisio_{July 7, 2015
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‘On’ switches for cells Researchers find early developmental signal hidden amid ‘noncoding’ RNA http://news.harvard.edu/gazette/story/2014/02/on-switches-for-cells/ Scientists at Harvard have identified a previously unknown embryonic signal, dubbed Toddler, that instructs cells to move and reorganize, through a process known as gastrulation, into three layers: the ectoderm, mesoderm, and endoderm. The new signal is described in a Jan. 9 paper in the journal Science. “The thought in the field — and I was one of the people who believed this — was that all the signals that regulate early development had been found,” he continued. “The discovery of Toddler suggests that other uncharacterized signals might still be out there.”

The thought in the field was wrong. What else is new?Dionisio_{July 7, 2015
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Olfactomedin-1 Has a V-shaped Disulfide-linked Tetrameric Structure* Matti F. Pronker‡, Trusanne G. A. A. Bos‡, Thomas H. Sharp§, Dominique M. E. Thies-Weesie¶ and Bert J. C. Janssen‡1 doi: 10.1074/jbc.M115.653485 The Journal of Biological Chemistry, 290, 15092-15101. http://www.jbc.org/content/290/24/15092.full?sid=e170ce96-e88d-4cbf-b4f3-fd3b4de9ef6d Olfm1 is an important signaling protein in the developing and adult nervous system. It is not known how Olfm1 regulates these processes, [...] How Olfm1 interacts with this diverse set of proteins and how this leads to signaling events that control neuronal developments are not clear. However, it is not clear how Olfm1 or the paralog (Olfm2, -3, and -4) oligomers are structurally arranged. The structure of Olfm1 and its paralogs is not known. It is not clear how the domains are arranged, which interactions mediate oligomerization, or whether it adopts a defined quaternary structure. Olfm1 can form stable homotetramers and likely also does so in vivo. [...] the detailed structure of the NTT domain and a portion of the coiled coil remain elusive. Whether the calcium is only structurally stabilizing the protein or serves a regulatory purpose remains to be determined. Whether other olfactomedin domain-containing proteins such as Olfm3 or myocilin could have a similar role in ion channel stabilization or regulation needs further investigation. This sheds light on the structure and quaternary organization of full-length Olfm1 as well as family members and provides new insights into function.
Some outstanding questions answered, newer issues raised. Work in progress... stay tuned.Dionisio_{July 7, 2015
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Regulator of G Protein Signaling 14: A Molecular Brake on Synaptic Plasticity Linked to Learning and Memory Paul R. Evans*, Serena M. Dudek†, John R. Hepler*, doi:10.1016/bs.pmbts.2015.03.006 Progress in Molecular Biology and Translational Science Volume 133, 2015, Pages 169–206 RGS Protein Physiology and Pathophysiology http://www.sciencedirect.com/science/article/pii/S1877117315000599 The regulators of G protein signaling (RGS) proteins are a diverse family of proteins that function as central components of G protein and other signaling pathways. In the brain, regulator of G protein signaling 14 (RGS14) is enriched in neurons in the hippocampus where the mRNA and protein are highly expressed. This brain region plays a major role in processing learning and forming new memories. RGS14 is an unusual RGS protein that acts as a multifunctional scaffolding protein to integrate signaling events and pathways essential for synaptic plasticity, including conventional and unconventional G protein signaling, mitogen-activated protein kinase, and, possibly, calcium signaling pathways. Principal neurons within the CA2 subfield differ from neighboring hippocampal regions in that they lack a capacity for long-term potentiation (LTP) of synaptic transmission, which is widely viewed as the cellular substrate of learning and memory formation. RGS14 was recently identified as a natural suppressor of LTP in hippocampal CA2 neurons as well as forms of learning and memory that depend on the hippocampus. Although CA2 has only recently been studied, compelling recent evidence implicates area CA2 as a critical component of hippocampus circuitry with functional roles in mediating certain types of learning and memory. This review will highlight the known functions of RGS14 in cell signaling and hippocampus physiology, and discuss potential roles for RGS14 in human cognition and disease.
Complex complexity :)Dionisio_{July 7, 2015
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Interplay of Cell Shape and Division Orientation Promotes Robust Morphogenesis of Developing Epithelia Fengzhu Xiong1, Wenzhe Ma1, Tom W. Hiscock1, Kishore R. Mosaliganti1, Andrea R. Tentner1, Kenneth A. Brakke2, Nicolas Rannou1, Arnaud Gelas1, Lydie Souhait1, Ian A. Swinburne1, Nikolaus D. Obholzer1, Sean G. Megason Volume 159, Issue 2, Pages 415–427 doi:10.1016/j.cell.2014.09.007 • Tissue geometry and cell mechanics constrain cell shapes in developing epithelia • Integrated mathematical model recapitulates dynamics of cell shape/number change • Interplay between cell shapes and division orientation ensures robust morphogenesis • Cell shape/division orientation relation may be tuned to give epithelial diversity Epithelial cells acquire functionally important shapes (e.g., squamous, cuboidal, columnar) during development. under geometrical constraints, pre-EVL flattening is regulated by surface cell number changes following differentially oriented cell divisions. The division pattern is, in turn, determined by the cell shape distribution, which forms under geometrical constraints by cell-cell mechanical coupling. An integrated mathematical model of this shape-division feedback loop recapitulates empirical observations. Surprisingly, the model predicts that cell shape is robust to changes of tissue surface area, cell volume, and cell number, which we confirm in vivo. Further simulations and perturbations suggest the parameter linking cell shape and division orientation contributes to epithelial diversity. http://www.sciencedirect.com/science/article/pii/S0092867414011556 http://www.ncbi.nlm.nih.gov/pubmed/25303534
Work in progress... stay tuned.Dionisio_{July 7, 2015
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Cell lineage tracing in the developing enteric nervous system: superstars revealed by experiment and simulation Bevan L. Cheeseman, Dongcheng Zhang, Benjamin J. Binder, Donald F. Newgreen, Kerry A. Landman DOI: 10.1098/rsif.2013.0815 http://rsif.royalsocietypublishing.org/content/11/93/20130815.full [...] the impact of spatial components on individual cell dynamics and resulting cell lineages needs to be determined. The ENC lineage tracing implies that self-organization principles of ENS development are predictable at the population level, but show stochastic diversity at the level of individual cells. [...] cell differentiation occurs after colonization, as stochastic competition for resources would permit early fate decisions to lead to highly unpredictable cell-fate distributions. [...] stochastic competition for resources (e.g. space, growth factor, nutrient) is fundamental to a proliferating invading cell population. [...] it seems likely that cell fate is determined after the migration wave process, and that local environment-based cell decisions at a later stage results in the highly regular cell-type proportions that are observed in developed ENS. [...] in any developmental system with early fate decisions, tight regulation between intercellular spatial distributions and proliferation cycles would seem to be required to preserve cell-type proportions.
tight regulation between intercellular spatial distributions and proliferation cycles would seem to be required How exactly is that 'tight regulation' done? Important issues remain unresolved. Work in progress... stay tuned.Dionisio_{July 7, 2015
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Ectopic Expression Screen Identifies Genes Affecting Drosophila Mesoderm Development Including the HSPG Trol Nathanie Trisnadi and Angelike Stathopoulos doi: 10.1534/g3.114.015891 G3 2015 vol. 5 no. 2 301-313 http://www.g3journal.org/content/5/2/301.full Some results were expected and others provide novel insight into this process. [...] overexpression of Ptp99a resulted in a moderate mesoderm phenotype; however, whether this relates to CSPG activity is unclear but possible. FGF signaling regulates a variety of activities that include communication between both distant cells and adjacent cells. However, their ability to modulate the range of FGF signaling is undetermined. A future direction would be to examine whether their differential roles relate to how each HSPG affects FGF ligand distribution.
A few questions remain unanswered. Work in progress... stay tuned.Dionisio_{July 5, 2015
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Growth factors and early mesoderm morphogenesis Ashrifia Adomako-Ankomah† and Charles A. Ettensohn* DOI: 10.1002/dvg.22746 http://onlinelibrary.wiley.com/doi/10.1002/dvg.22746/full genesis Special Issue: Sea Urchin Special Issue Volume 52, Issue 3, pages 158–172 The directional movements of mesoderm cells are among the most prominent features of gastrulation. An exciting finding from recent studies is that, in organisms as diverse as fruit flies, sea urchins, and vertebrates, growth factors play an essential role in these movements. Growth factors do not seem to be strictly required for mesoderm motility; rather, their principal function is to orient the movements of cells within a complex extracellular matrix. Surprisingly, the principal ligands (and their cognate receptors) that regulate early mesoderm morphogenesis vary among organisms, revealing considerable evolutionary flexibility in this developmental program. Clearly, further analysis of FGF signaling in other sea urchins is needed. Growth factor signaling may not be the only mechanism by which the ectoderm regulates PMC migration and differentiation. At present, it is not known whether these molecules act by regulating VEGF expression and/or function, or by completely independent mechanisms. Growth factors have diverse effects on cells, and one general challenge is to distinguish the effects of signaling pathways on cell movements from their effects on cell differentiation, to the extent that these are separable. Other experimental challenges are presented by the multiplicity of potential ligands and receptors (which are typically members of small gene families) and the possibility of crosstalk among them, factors that complicate the design and interpretation of gene knockdown and chemical inhibitor studies. To deepen our understanding of the function of growth factor signaling pathways in mesoderm morphogenesis, it will be important to elucidate the downstream effectors of these pathways. The extent to which these same signaling pathways operate in early embryonic cells that are responding to growth factors is an intriguing and open question.
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