Mystery at the heart of life

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December 21, 2014

Cell biology, Intelligent Design, News

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Cell biology
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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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Ectopic Expression Screen Identifies Genes Affecting Drosophila Mesoderm Development Including the HSPG Trol Nathanie Trisnadi and Angelike Stathopoulos doi: 10.1534/g3.114.015891 http://www.g3journal.org/content/5/2/301.full
Gastrulation of the embryo involves coordinate cell movements likely supported by multiple signaling pathways, adhesion molecules, and extracellular matrix components. Fibroblast growth factors (FGFs) have a major role in Drosophila melanogaster mesoderm migration; however, few other inputs are known and the mechanism supporting cell movement is unclear. 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.

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Ezh2 maintains retinal progenitor proliferation, transcriptional integrity, and the timing of late differentiation Jianmin Zhanga, Russell J. Taylorb, Anna La Torreb, Matthew S. Wilkenb, c, Kristen E. Coxb, Thomas A. Rehb, Monica L. Vetter doi:10.1016/j.ydbio.2015.05.010 Developmental Biology Volume 403, Issue 2, Pages 128–138 http://www.sciencedirect.com/science/article/pii/S0012160615002791
Epigenetic regulation, including histone modification, is a critical component of gene regulation, although precisely how this contributes to the development of complex tissues such as the neural retina is still being explored.

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Regulation of Peripheral Nerve Myelin Maintenance by Gene Repression through Polycomb Repressive Complex 2 Ki H. Ma, Holly A. Hung, Rajini Srinivasan, Huafeng Xie, Stuart H. Orkin, and John Svaren The Journal of Neuroscience, 35(22): 8640-8652; doi: 10.1523/JNEUROSCI.2257-14.2015 http://www.jneurosci.org/content/35/22/8640.short
Myelination of peripheral nerves by Schwann cells requires coordinate regulation of gene repression as well as gene activation. Several chromatin remodeling pathways critical for peripheral nerve myelination have been identified, but the functions of histone methylation in the peripheral nerve have not been elucidated.

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Atypical regulation of G protein-coupled receptor intracellular trafficking by ubiquitination Michael R. Dores and JoAnn Trejo doi:10.1016/j.ceb.2013.11.004 Current Opinion in Cell Biology Volume 27, Pages 44–50 Cell regulation http://www.sciencedirect.com/science/article/pii/S0955067413001804
Unlike the canonical ESCRT-dependent lysosomal sorting pathway, the mechanisms that regulate ALIX-mediated GPCR degradation are not known. It is possible that ALIX or ARRDC binding partners recruit E3 ubiquitin ligases to facilitate lysosomal sorting of YPXnL-motif containing GPCRs, however the role of ARRDCs in the ubiquitination of ALIX, and the lysosomal sorting of YPXnL-motif GPCRs has yet to be determined. ALIX binds to lysobisphosphatidic acid (LBPA), a unique lipid enriched at late endosomal membranes [50], and is important for its function, but how LBPA affects ALIX activity is not known. The challenge now is to determine how GASP-1 and ALIX engage with ubiquitin and ESCRTs to mediate GPCR lysosomal degradation. GASP-1 and ALIX selectively regulate individual members of GPCR subfamilies, particularly those that are efficiently sorted to lysosomes and not recycled, but the underlying basis for this is not known.

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Endocytosis and Signaling during Development Christian Bökel and Michael Brand doi: 10.1101/cshperspect.a017020 http://cshperspectives.cshlp.org/content/6/3/a017020.abstract
The development of multicellular organisms relies on an intricate choreography of intercellular communication events that pattern the embryo and coordinate the formation of tissues and organs. Cell biologists may in the future want to increasingly appreciate the complexity of the signaling environment that governs the behavior of the cells they study. This complexity includes not only the organization of the signaling cascades themselves but also their regulation at the cell biological level. Both must be taken into account in an organismal context. In addition to and beyond the established cell culture systems, signal transduction should therefore increasingly be studied in vivo, focusing on specific cell types in their natural environments within a developing model organism. Conversely, developmental biology can only gain from studying how morphogen gradient formation and interpretation is implemented at the subcellular level. Studying morphogenetic pattern formation at the level of expression patterns of ligands, receptors, and target genes will in the long run not be enough. To fully understand how developmental signals are generated, processed, and interpreted to eventually generate morphogenetic information, the role of cell biological processes such as endocytosis and subcellular trafficking as rheostats of signal transduction must be increasingly taken into account.

That's a brief “to-do list” for developmental and cell biology. A few questions remain unanswered. Work in progress... stay tuned.Dionisio_{August 18, 2015
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Signal Transduction: From the Atomic Age to the Post-Genomic Era Jeremy Thorner, Tony Hunter, Lewis C. Cantley and Richard Sever doi: 10.1101/cshperspect.a022913 http://cshperspectives.cshlp.org/content/6/12/a022913.abstract
[...] it is important to consider how fast this field is still moving and the issues at the current boundaries of our understanding. We summarize here some key issues (both conceptual and methodological), raise unresolved questions, discuss potential pitfalls, and highlight areas in which our understanding is still rudimentary. We hope these wide-ranging ruminations will be useful to investigators who carry studies of signal transduction forward during the rest of the 21st century.

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Signaling Mechanisms Controlling Cell Fate and Embryonic Patterning Norbert Perryman, Chrysoula Pitsouli and Ben-Zion Shilo doi: 10.1101/cshperspect.a005975 http://cshperspectives.cshlp.org/content/4/8/a005975.abstract
How Notch signaling, especially considering the simplicity of the pathway, specifies so many different biological outcomes, depending on the cell context, is a major question in the field

Amazing functional complexity. Excellent paper.Dionisio_{August 18, 2015
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Shaping Morphogen Gradients by Proteoglycans Dong Yan and Xinhua Lin doi: 10.1101/cshperspect.a002493 http://cshperspectives.cshlp.org/content/1/3/a002493.full
Although HSPGs can be regulated by various shedding mechanisms, the in vivo roles of HSPG shedding are largely unknown. In particular, how this process contributes to morphogen gradient formation awaits further investigations. Given the molecular complexity of HSPGs, further understanding of HSPG functions in morphogen signaling and distribution will require the combination of genetic, cell biological, and biochemical approaches. Determination of HS structures of specific HSPGs by HS GAG sequencing and by advanced mass spectroscopy technique will help elucidate the molecular nature of HSPG-morphogen interactions. Moreover, determination of glypican core protein structures by X-ray crystallography will allow us to define the interaction of glypican core and specific morphogen molecules. Finally, characterization of specific extracellular and cell surface proteins interacting with HSPGs will further our understanding of the mechanisms by which these cell surface proteins modulate morphogen gradient.

Work in progress... stay in tune.Dionisio_{August 18, 2015
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#820 follow up (2)
With more details on plant stem cell control emerging, it will be exciting to see whether additional shared molecular mechanisms will be identified. Although a number of different molecular pathways have been shown to contribute to QC cell quiescence, it remains to be deciphered how they are interconnected to control self-renewal of the QC. However, it still remains unclear whether the connection between WUS and chromatin remodelling through histone de-acetylation plays a role for shoot stem cell pluripotency. This raises important questions regarding the molecular control and the sequence of cellular events acting downstream of auxin signalling during cell fate re-specification and tissue regeneration. Further investigations are therefore required to fully clarify the role of differentiated plant cells during tissue reprogramming towards a pluripotent state. It will be imperative to further decode the mechanisms by which environmental and metabolic signals impinge on this regulatory program and to understand how this is translated into cell behaviour. In this context, more research is required to elucidate the nature and position of these cells and to delineate the signals leading to their activation. Again, our appreciation of the signals encoding this spatio-temporal information is still limited and requires further refinement.
The never-ending story: from pluripotency to plant developmental plasticity Christophe Gaillochet and Jan U. Lohmann doi: 10.1242/dev.117614 Development 142, 2237-2249. http://dev.biologists.org/content/142/13/2237.full

As outstanding questions get answered, new ones are raised. Unending Revelation of the Ultimate RealityDionisio_{August 18, 2015
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#820 follow up (1)
[...] how this network responds to environmental signals and how these inputs are translated into cellular behaviour ultimately leading to plant developmental plasticity still remains to be elucidated. Recent studies have begun to elucidate the organisation of the SAM and the RAM, and the key mechanisms that regulate these stem cell niches.
The never-ending story: from pluripotency to plant developmental plasticity Christophe Gaillochet and Jan U. Lohmann doi: 10.1242/dev.117614 Development 142, 2237-2249. http://dev.biologists.org/content/142/13/2237.full

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The never-ending story: from pluripotency to plant developmental plasticity Christophe Gaillochet and Jan U. Lohmann doi: 10.1242/dev.117614 Development 142, 2237-2249. http://dev.biologists.org/content/142/13/2237.short?rss=1&ssource=mfr
[...] the mechanisms regulating fate transitions must be continuously active in most plant cells and that the control of cellular pluripotency lies at the core of diverse developmental programs.

Unending Revelation of the Ultimate Reality [B:(H&O+E&T+A&S+J&H+A&R+M&M)]@K/150818!Dionisio_{August 17, 2015
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Cytoneme-mediated cell-to-cell signaling during development Ana-Citlali Gradilla, Isabel Guerrero Cell and Tissue Research Volume 352, Issue 1, pp 59-66 http://link.springer.com/article/10.1007%2Fs00441-013-1578-x
Cell-to-cell communication is vital for animal tissues and organs to develop and function as organized units. Throughout development, intercellular communication is crucial for the generation of structural diversity, mainly by the regulation of differentiation and growth. During these processes, several signaling molecules function as messengers between cells and are transported from producing to receptor cells. Thus, a tight spatial and temporal regulation of signaling transport is likely to be critical during morphogenesis. Despite much experimental and theoretical work, the question as to how these signals move between cells remains. Cell-to-cell contact is probably the most precise spatial and temporal mechanism for the transference of signaling molecules from the producing to the receiving cells. However, most of these molecules can also function at a distance between cells that are not juxtaposed. Recent research has shown the way in which cells may achieve direct physical contact and communication through actin-based filopodia. In addition, increasing evidence is revealing the role of such filopodia in regulating spatial patterning during development; in this context, the filopodia are referred to as cytonemes. The processes that initiate and regulate the formation, orientation and dynamics of cytonemes are poorly understood but are potentially extremely important areas for our knowledge of intercellular communication.

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Morphogen Gradient Formation Ortrud Wartlick, Anna Kicheva and Marcos González-Gaitán doi: 10.1101/cshperspect.a001255 http://cshperspectives.cshlp.org/content/1/3/a001255.full#sec-14
How morphogen gradients are formed in target tissues is a key question for understanding the mechanisms of morphological patterning. How a multicellular organism develops from a single fertilized cell has fascinated people throughout history. mutant analysis revealed the importance of the underlying cell biology and the different molecules necessary to produce, move, and degrade morphogens. In the future, progress will derive from a similar type of physical, theoretical, and experimental approach at the cellular and subcellular levels: How morphogens and their receptors are moving inside cells and at the extracellular matrix.

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Direct Delivery Mechanisms of Morphogen Dispersion Sougata Roy and Thomas B. Kornberg Science Signaling Vol. 4, Issue 200, pp. pt8 DOI: 10.1126/scisignal.2002434 http://stke.sciencemag.org/content/4/200/pt8
Although the steady-state distributions of morphogen signaling proteins have been described well in a number of contexts, the mechanisms that generate these distributions have remained uncertain. [...] these proteins transfer from producing to target cells at points of direct contact, even when the producing and target cells are not immediate neighbors.

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Paracrine signaling mediated at cell–cell contacts Sougata Roy†,* and Thomas B. Kornberg DOI: 10.1002/bies.201400122 BioEssays Volume 37, Issue 1, pages 25–33, http://onlinelibrary.wiley.com/doi/10.1002/bies.201400122/full
Recent findings in several organ systems show that cytoneme-mediated signaling transports signaling proteins along cellular extensions and targets cell-to-cell exchanges to synaptic contacts. This mechanism of paracrine signaling may be a general one that is used by many (or all) cell types in many (or all) organs. We briefly review these findings in this perspective. We also describe the properties of several signaling systems that have previously been interpreted to support a passive diffusion mechanism of signaling protein dispersion, but can now be understood in the context of the cytoneme mechanism. For both the vertebrate and Drosophila systems, a better understanding of the structure of the ECM, of the role and structure of cytonemes, and of the state of in transit signaling proteins is needed in order to know if the apparent differences reflect different mechanisms. In the absence of evidence for or against the presence of signal protein-carrying cytonemes, conclusions should reflect the uncertainties that the state of understanding demands.

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Mobility of signaling molecules: the key to deciphering plant organogenesis Kensuke Kawade, and Hirokazu Tanimoto Journal of Plant Research 128:692 DOI: 10.1007/s10265-014-0692-5 JPR Symposium Plasmodesmata: Function and Diversity in Plant Intercellular Communication http://link.springer.com/article/10.1007/s10265-014-0692-5/fulltext.html
Signaling molecules move between cells to form a characteristic distribution pattern within a developing organ; thereafter, they spatiotemporally regulate organ development. A key question in this process is how the signaling molecules robustly form the precise distribution on a tissue scale in a reproducible manner. Despite of an increasing number of quantitative studies regarding the mobility of signaling molecules, the detail mechanism of organogenesis via intercellular signaling is still unclear. Our next challenge is to assess the dynamics of signaling molecules at a larger scale (global diffusivity) to explain the mechanisms by which the tissue-scale distribution of signaling molecules is established during organogenesis, and its control of developmental progression. The wealth of quantitative imaging techniques, together with a unique mode of intercellular signaling in plants, will allow us to decipher the puzzle of organogenesis via intercellular signaling.

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Cytonemes and the dispersion of morphogens Thomas B. Kornberg* DOI: 10.1002/wdev.151 Wiley Interdisciplinary Reviews: Developmental Biology Volume 3, Issue 6, pages 445–463 http://onlinelibrary.wiley.com/doi/10.1002/wdev.151/abstract
Filopodia are cellular protrusions that have been implicated in many types of mechanosensory activities. Morphogens are signaling proteins that regulate the patterned development of embryos and tissues. Both have long histories that date to the beginnings of cell and developmental biology in the early 20th century, but recent findings tie specialized filopodia called cytonemes to morphogen movement and morphogen signaling. This review explores the conceptual and experimental background for a model of paracrine signaling in which the exchange of morphogens between cells is directed to sites where cytonemes directly link cells that produce morphogens to cells that receive and respond to them. WIREs Dev Biol 2014, 3:445–463. doi: 10.1002/wdev.151

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Bending Gradients: How the Intestinal Stem Cell Gets Its Home Amy E. Shyer1, Tyler R. Huycke, ChangHee Lee, L. Mahadevan, Clifford J. Tobin. Cell Volume 161, Issue 3, Pages 569–580 doi:10.1016/j.cell.2015.03.041 http://www.sciencedirect.com/science/article/pii/S009286741500361X
Highlights • The entire embryonic gut epithelium expresses intestinal stem cell (ISC) markers • As villi form, BMP activity from underlying mesenchyme restricts ISCs to their base • The mesenchymal Bmp expression is induced at villus tips by Shh from the endoderm • Uniformly secreted Shh is concentrated by the physically driven villus architecture
Summary We address the mechanism by which adult intestinal stem cells (ISCs) become localized to the base of each villus during embryonic development. We find that, early in gut development, proliferating progenitors expressing ISC markers are evenly distributed throughout the epithelium, in both the chick and mouse. However, as the villi form, the putative stem cells become restricted to the base of the villi. This shift in the localization is driven by mechanically influenced reciprocal signaling between the epithelium and underlying mesenchyme. Buckling forces physically distort the shape of the morphogenic field, causing local maxima of epithelial signals, in particular Shh, at the tip of each villus. This induces a suite of high-threshold response genes in the underlying mesenchyme to form a signaling center called the “villus cluster.” Villus cluster signals, notably Bmp4, feed back on the overlying epithelium to ultimately restrict the stem cells to the base of each villus.

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Gradients Are Shaping Up Tobias Bollenbach, Carl-Philipp Heisenberg doi:10.1016/j.cell.2015.04.009 Volume 161, Issue 3, Pages 431–432 http://www.sciencedirect.com/science/article/pii/S0092867415004262
In animal embryos, morphogen gradients determine tissue patterning and morphogenesis. Shyer et al. provide evidence that, during vertebrate gut formation, tissue folding generates graded activity of signals required for subsequent steps of gut growth and differentiation, thereby revealing an intriguing link between tissue morphogenesis and morphogen gradient formation.

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Spatiotemporal Analysis of Different Mechanisms for Interpreting Morphogen Gradients David M. Richards, Timothy E. Saunders Biophysical Journal Volume 108, Issue 8, Pages 2061–2073 doi:10.1016/j.bpj.2015.03. http://www.sciencedirect.com/science/article/pii/S0006349515002751
During development, multicellular organisms must accurately control both temporal and spatial aspects of tissue patterning. This is often achieved using morphogens, signaling molecules that form spatially varying concentrations and so encode positional information. Typical analysis of morphogens assumes that spatial information is decoded in steady state by measuring the value of the morphogen concentration. However, recent experimental work suggests that both pre-steady-state readout and measurement of spatial and temporal derivatives of the morphogen concentration can play important roles in defining boundaries.

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ESCRT Function in Cytokinesis: Location, Dynamics and Regulation by Mitotic Kinases Musab S. Bhutta, Christopher J. McInerny and Gwyn W. Gould Int. J. Mol. Sci., 15(12), 21723-21739; doi:10.3390/ijms151221723 http://www.mdpi.com/1422-0067/15/12/21723/htm
A key goal of cell and developmental biologists is to develop a clear understanding of the mechanisms that underpin abscission, and how the spatiotemporal coordination of these events with previous stages in cell division is accomplished. This requires the assembly of the abscission machine with absolutely precise spatial and temporal coordinates. The role of ESCRTs in abscission is firmly established. How these interesting proteins functionally cooperate in space and time in response to defined signals remains only partly understood. it is clear that phospho-regulation, and the protein kinases and phosphatases that regulate these events, will form a significant component of the future research into ESCRT proteins.

As advancing research sheds more light on the elaborate cellular and molecular choreographies orchestrated within the biological systems, outstanding questions get answered while new ones are raised. As the big picture of the biological puzzle turns more clear, its complexity appears more complex with every discovery.Dionisio_{August 12, 2015
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Specific Localization of the Drosophila Telomere Transposon Proteins and RNAs, Give Insight in Their Behavior, Control and Telomere Biology in This Organism Elisenda López-Panadès, Elizabeth R. Gavis, Elena Casacuberta PLOS •DOI: 10.1371/journal.pone.0128573 http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0128573
our current understanding of how the mechanism of the retrotransposon telomere works and which features are shared with the telomerase system is very limited.

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Cell collectivity regulation within migrating cell cluster during Kupffer's vesicle formation in zebrafish Takaaki Matsui*, Hiroshi Ishikawa and Yasumasa Bessho Front. Cell Dev. Biol., 07 May 2015 | http://dx.doi.org/10.3389/fcell.2015.00027 http://journal.frontiersin.org/article/10.3389/fcell.2015.00027/abstract
[...] mechanisms of cells staying assembled as a single cell cluster, termed as “cell collectivity,” remain largely unknown. [...] multicellular tissues/organs are more dynamic than previously thought. Despite this substantial progress, many important questions remain. how do collective cell dynamics contribute to generating functional organs? How does the pairing of tight junction change? Are adherens junctions, tight junctions, and cell-ECM interaction coordinated? Does mechanical force contribute to collective DFC migration? Does collective DFC migration have analogy with other collective cell migrations seen in normal development, wound repair, and cancer invasion? It is of great interest to fill in these gaps to further clarify the regulatory mechanisms and importance of collective cell migration during organogenesis.

As advancing research sheds more light on the elaborate cellular and molecular choreographies orchestrated within the biological systems, outstanding questions get answered while new ones are raised. As the big picture of the biological puzzle turns more clear, its complexity appears more complex with every discovery.Dionisio_{August 12, 2015
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A Mathematical Model of Collective Cell Migration in a Three-Dimensional, Heterogeneous Environment David P. Stonko, Lathiena Manning, Michelle Starz-Gaiano, Bradford E. Peercy PLOS •DOI: 10.1371/journal.pone.0122799 http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0122799
Cell migration is essential in animal development, homeostasis, and disease progression, but many questions remain unanswered about how this process is controlled. The process of collective cell migration that occurs during Drosophila oogenesis is a highly regulated, complex system. A future research interest is to integrate more molecular signaling data into the biophysical model in an effort to recapitulate additional in vivo behaviors.

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Tissue landscape alters adjacent cell fates during Drosophila egg development Lathiena A. Manning, Ann Marie Weideman, Bradford E. Peercy & Michelle Starz-Gaiano Nature Communications 6, Article number: 7356 doi:10.1038/ncomms8356 http://www.nature.com/ncomms/2015/150617/ncomms8356/full/ncomms8356.html
Extracellular signalling molecules control many biological processes, but the influence of tissue architecture on the local concentrations of these factors is unclear.

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#796 follow up (9)
Group choreography: mechanisms orchestrating the collective movement of border cells Denise J. Montell, Wan Hee Yoon & Michelle Starz-Gaiano Nature Reviews Molecular Cell Biology 13, 631-645 doi:10.1038/nrm3433 http://www.nature.com/nrm/journal/v13/n10/full/nrm3433.html Nat Rev Mol Cell Biol. Author manuscript; available in PMC 2014 Jul 15.
A broader open question is whether each collective cell movement is a unique performance with a choreography of its own, or whether there might be a repertoire of subroutines that can be combined in different ways to generate diversity. Repeated use of proteins such as RAC in different motile cell types, both collective and individual, suggests that there is a repertoire of functional modules, so the challenge will be to determine what they are and how they are combined in different ways to produce just the right performance for each cell type and biological setting. Now that molecules with either major or supporting roles in collective cell migration have been identified, current challenges are to decipher how mechanical forces and biochemical signals are integrated and feed back to one another to coordinate protrusion, contractility, cell–cell and cell–ECM adhesion in space and time at subcellular, cellular and multicellular scales.

That's quite a "finale" for an excellent review paper.Dionisio_{August 12, 2015
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#796 follow up (8)
Group choreography: mechanisms orchestrating the collective movement of border cells Denise J. Montell, Wan Hee Yoon & Michelle Starz-Gaiano Nature Reviews Molecular Cell Biology 13, 631-645 doi:10.1038/nrm3433 http://www.nature.com/nrm/journal/v13/n10/full/nrm3433.html Nat Rev Mol Cell Biol. Author manuscript; available in PMC 2014 Jul 15.
Many interesting questions remain unanswered and present opportunities for the future. Key open questions include how the lead cell communicates with the following cells (via biochemical signals, mechanical forces or some combination of the two) to achieve coordinated directional behaviour. Elucidating the complete biochemical pathways from guidance receptors to small GTPases, F-actin regulators and adhesion molecules will also be important and has yet to be fully defined even in cultured cells. Unravelling the crosstalk between RHO, RAC and CDC42 in this in vivo context may contribute significant new insights into the functions of these crucial regulators of protrusion, adhesion and contractility. Although it is clear that border cells can change positions during migration so that new leaders emerge, it is less clear what the causes and functional importance of this behaviour are.

As advancing research sheds more light on the elaborate cellular and molecular choreographies orchestrated within the biological systems, outstanding questions get answered while new ones are posed. As the big picture of the biological puzzle turns more clear, its complexity appears more complex with every discovery. Let's encourage and motivate young students to pursue exciting careers in biology-related fields. The increasing Big Data conundrum requires more dedicated researchers to collaborate in multidisciplinary teams.Dionisio_{August 12, 2015
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#796 follow up (7)
Group choreography: mechanisms orchestrating the collective movement of border cells Denise J. Montell, Wan Hee Yoon & Michelle Starz-Gaiano Nature Reviews Molecular Cell Biology 13, 631-645 doi:10.1038/nrm3433 http://www.nature.com/nrm/journal/v13/n10/full/nrm3433.html Nat Rev Mol Cell Biol. Author manuscript; available in PMC 2014 Jul 15.
Migrating cells are a tremendously diverse set of soloists and ensembles that move through an ever-changing scenery, and we are really only just beginning to elucidate how they are selected and directed, how they keep time and they coordinate their steps. Signalling pathways with intricate feedback loops carry out the crucial function of specifying the migratory population and ensuring proper developmental timing. Guidance cues, adhesion molecules and cytoskeletal regulators control spatially segregated protrusion, adhesion and retraction events that propel the cells in the correct direction.

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#796 follow up (6)
Group choreography: mechanisms orchestrating the collective movement of border cells Denise J. Montell, Wan Hee Yoon & Michelle Starz-Gaiano Nature Reviews Molecular Cell Biology 13, 631-645 doi:10.1038/nrm3433 http://www.nature.com/nrm/journal/v13/n10/full/nrm3433.html Nat Rev Mol Cell Biol. Author manuscript; available in PMC 2014 Jul 15.
Studies of border cells have led to several surprises, including the finding that some proteins, such as ENA, have unforeseen or more complex roles in migration and the discovery of new players in basic actin dynamics. More studies are needed to elucidate precisely how cytoskeletal changes are governed in different migratory cell types.

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#796 follow up (5)
Group choreography: mechanisms orchestrating the collective movement of border cells Denise J. Montell, Wan Hee Yoon & Michelle Starz-Gaiano Nature Reviews Molecular Cell Biology 13, 631-645 doi:10.1038/nrm3433 http://www.nature.com/nrm/journal/v13/n10/full/nrm3433.html Nat Rev Mol Cell Biol. Author manuscript; available in PMC 2014 Jul 15.
Together, these findings suggest that the precise contribution of each actin regulatory protein to motility varies from one cell type to another, probably due to the different combinations of various actin regulatory proteins present in each cell type, some of which have overlapping activities.

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