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Takashi Namba, Samir Vaid, Wieland Huttner
Primate neocortex development and evolution: Conserved versus evolved folding.
J Comp Neurol, 527(10) 1621-1632 (2019)
PubMed Source   

The neocortex, the seat of higher cognitive functions, exhibits a key feature across mammalian species-a highly variable degree of folding. Within the neocortex, two distinct subtypes of cortical areas can be distinguished, the isocortex and the proisocortex. Here, we have compared specific spatiotemporal aspects of folding between the proisocortex and the isocortex in 13 primates, including human, chimpanzee, and various Old World and New World monkeys. We find that folding at the boundaries of the dorsal isocortex and the proisocortex, which gives rise to the cingulate sulcus (CiS) and the lateral fissure (LF), is conserved across the primates studied and is therefore referred to as conserved folding. In contrast, the degree of folding within the dorsal isocortex exhibits huge variation across these primates, indicating that this folding, which gives rise to gyri and sulci, is subject to major changes during primate evolution. We therefore refer to the folding within the dorsal isocortex as evolved folding. Comparison of fetal neocortex development in long-tailed macaque and human reveals that the onset of conserved folding precedes the onset of evolved folding. Moreover, the analysis of infant human neocortex exhibiting lissencephaly, a developmental malformation thought to be mainly due to abnormal neuronal migration, shows that the evolved folding is perturbed more than the conserved folding. Taken together, our study presents a two-step model of folding that pertains to primate neocortex development and evolution. Specifically, our data imply that the conserved folding and the evolved folding constitute two distinct, sequential events.
@article{Namba7305,
author={Takashi Namba, Samir Vaid, Wieland Huttner},
title={Primate neocortex development and evolution: Conserved versus evolved folding.},
journal ={The Journal of comparative neurology},
volume={527},
issue ={10},
pages={1621--1632},
year=2019
}

João P L Castro, Michelle N Yancoskie, Marta Marchini, Stefanie Belohlavy, Layla Hiramatsu, Marek Kučka, William H Beluch, Ronald Naumann, Isabella Skuplik, John Cobb, Nick H Barton, Campbell Rolian, Yingguang Frank Chan
An integrative genomic analysis of the Longshanks selection experiment for longer limbs in mice.
Elife, 8 Art. No. doi: 10.7554/eLife.42014 (2019)
PubMed Source   

Evolutionary studies are often limited by missing data that are critical to understanding the history of selection. Selection experiments, which reproduce rapid evolution under controlled conditions, are excellent tools to study how genomes evolve under selection. Here we present a genomic dissection of the Longshanks selection experiment, in which mice were selectively bred over 20 generations for longer tibiae relative to body mass, resulting in 13% longer tibiae in two replicates. We synthesized evolutionary theory, genome sequences and molecular genetics to understand the selection response and found that it involved both polygenic adaptation and discrete loci of major effect, with the strongest loci tending to be selected in parallel between replicates. We show that selection may favor de-repression of bone growth through inactivating two limb enhancers of an inhibitor, Nkx3-2. Our integrative genomic analyses thus show that it is possible to connect individual base-pair changes to the overall selection response.
@article{Castro7408,
author={João P L Castro, Michelle N Yancoskie, Marta Marchini, Stefanie Belohlavy, Layla Hiramatsu, Marek Kučka, William H Beluch, Ronald Naumann, Isabella Skuplik, John Cobb, Nick H Barton, Campbell Rolian, Yingguang Frank Chan},
title={An integrative genomic analysis of the Longshanks selection experiment for longer limbs in mice.},
journal ={eLife},
volume={8},
pages={1--1},
year=2019
}

Ivana Viktorinová, Robert Haase, Tobias Pietzsch, Ian Henry, Pavel Tomancak
Analysis of Actomyosin Dynamics at Local Cellular and Tissue Scales UsingTime-lapse Movies of Cultured Drosophila Egg Chambers
J Vis Exp, 148 Art. No. e58587 (2019)
Source   

Drosophila immature eggs are called egg chambers, and their structure resembles primitive organs that undergo morphological changes from around to an ellipsoid shape during development. This developmental process is called oogenesis and is crucial to generating functional matureeggs to secure the next fly generation. For these reasons, egg chambers have served as an ideal and relevant model to understand animalorgan development.Several in vitro culturing protocols have been developed, but there are several disadvantages to these protocols. One involves the application ofvarious covers that exert an artificial pressure on the imaged egg chambers in order to immobilize them and to increase the imaged acquisitionplane of the circumferential surface of the analyzed egg chambers. Such an approach may negatively influence the behavior of the thinactomyosin machinery that generates the power to rotate egg chambers around their longer axis.Thus, to overcome this limitation, we culture Drosophila egg chambers freely in the media in order to reliably analyze actomyosin machineryalong the circumference of egg chambers. In the first part of the protocol, we provide a manual detailing how to analyze the actomyosinmachinery in a limited acquisition plane at the local cellular scale (up to 15 cells). In the second part of the protocol, we provide users with a newFiji-based plugin that allows the simple extraction of a defined thin layer of the egg chambers’ circumferential surface. The following protocol thendescribes how to analyze actomyosin signals at the tissue scale (>50 cells). Finally, we pinpoint the limitations of these approaches at both thelocal cellular and tissue scales and discuss its potential future development and possible applications.
@article{null7407,
author={Ivana Viktorinová, Robert Haase, Tobias Pietzsch, Ian Henry, Pavel Tomancak},
title={Analysis of Actomyosin Dynamics at Local Cellular and Tissue Scales UsingTime-lapse Movies of Cultured Drosophila Egg Chambers},
journal ={Journal of visualized experiments : JoVE},
volume={148},
pages={1--1},
year=2019
}

Dimitrios Papadopoulos, Pavel Tomancak
Gene Regulation: Analog to Digital Conversion of Transcription Factor Gradients.
Curr Biol, 29(11) 422-424 (2019)
PubMed Source   

Transcription factor gradients trigger differential transcriptional responses based on concentration. But how, in some cases, do target genes maintain uniform transcription across portions of the gradient? Lessons from Drosophila demonstrate that organization of transcription into 'hubs' can lead to local increases in transcription factor concentration.
@article{Papadopoulos7404,
author={Dimitrios Papadopoulos, Pavel Tomancak},
title={Gene Regulation: Analog to Digital Conversion of Transcription Factor Gradients.},
journal ={Current biology : CB},
volume={29},
issue ={11},
pages={422--424},
year=2019
}

Eugenia Marbach-Breitrück, Madlen Matz-Soja, Ute Abraham, Wolfgang Schmidt-Heck, Susanne Sales, Christiane Rennert, Matthias Kern, Susanne Aleithe, Luise Spormann, Carlo Thiel, Raffaele Gerlini, Katrin Arnold, Nora Klöting, Reinhard Guthke, Damjana Rozman, Raffaele Teperino, Andrej Shevchenko, Achim Kramer, Rolf Gebhardt
Tick-tock hedgehog-mutual crosstalk with liver circadian clock promotes liver steatosis.
J Hepatol, 70(6) 1192-1202 (2019)
PubMed Source   

The mammalian circadian clock controls various aspects of liver metabolism and integrates nutritional signals. Recently, we described Hedgehog (Hh) signaling as a novel regulator of liver lipid metabolism. Herein, we investigated crosstalk between hepatic Hh signaling and circadian rhythm.
@article{Marbach-Breitrück7353,
author={Eugenia Marbach-Breitrück, Madlen Matz-Soja, Ute Abraham, Wolfgang Schmidt-Heck, Susanne Sales, Christiane Rennert, Matthias Kern, Susanne Aleithe, Luise Spormann, Carlo Thiel, Raffaele Gerlini, Katrin Arnold, Nora Klöting, Reinhard Guthke, Damjana Rozman, Raffaele Teperino, Andrej Shevchenko, Achim Kramer, Rolf Gebhardt},
title={Tick-tock hedgehog-mutual crosstalk with liver circadian clock promotes liver steatosis.},
journal ={Journal of hepatology},
volume={70},
issue ={6},
pages={1192--1202},
year=2019
}

Volker Hartenstein, Michaela Yuan, Amelia Younossi-Hartenstein, Aanavi Karandikar, F Javier Bernardo-Garcia, Simon Sprecher, Elisabeth Knust
Serial electron microscopic reconstruction of the drosophila larval eye: Photoreceptors with a rudimentary rhabdomere of microvillar-like processes.
Dev Biol, Art. No. doi: 10.1016/j.ydbio.2019.05.017 (2019)
PubMed Source   

Photoreceptor cells (PRCs) across the animal kingdom are characterized by a stacking of apical membranes to accommodate the high abundance of photopigment. In arthropods and many other invertebrate phyla PRC membrane stacks adopt the shape of densely packed microvilli that form a structure called rhabdomere. PRCs and surrounding accessory cells, including pigment cells and lens-forming cells, are grouped in stereotyped units, the ommatidia. In larvae of holometabolan insects, eyes (called stemmata) are reduced in terms of number and composition of ommatidia. The stemma of Drosophila (Bolwig organ) is reduced to a bilateral cluster of subepidermal PRCs, lacking all other cell types. In the present paper we have analyzed the development and fine structure of the Drosophila larval PRCs. Shortly after their appearance in the embryonic head ectoderm, PRC precursors delaminate and lose expression of apical markers of epithelial cells, including Crumbs and several centrosome-associated proteins. In the early first instar larva, PRCs show an expanded, irregularly shaped apical surface that is folded into multiple horizontal microvillar-like processes (MLPs). Apical PRC membranes and MLPs are covered with a layer of extracellular matrix. MLPs are predominantly aligned along an axis that extends ventro-anteriorly to dorso-posteriorly, but vary in length, diameter, and spacing. Individual MLPs present a "beaded" shape, with thick segments (0.2-0.3 μm diameter) alternating with thin segments (>0.1 μm). We show that loss of the glycoprotein Chaoptin, which is absolutely essential for rhabdomere formation in the adult PRCs, does not lead to severe abnormalities in larval PRCs.
@article{Hartenstein7405,
author={Volker Hartenstein, Michaela Yuan, Amelia Younossi-Hartenstein, Aanavi Karandikar, F Javier Bernardo-Garcia, Simon Sprecher, Elisabeth Knust},
title={Serial electron microscopic reconstruction of the drosophila larval eye: Photoreceptors with a rudimentary rhabdomere of microvillar-like processes.},
journal ={Developmental biology},
volume={},
pages={1--1},
year=2019
}

Steven W Poser, Oliver Otto, Carina Arps-Forker, Yan Ge, Maik Herbig, Cordula Andree, Konrad Gruetzmann, Melissa F Adasme, Szymon Stodolak, Polyxeni Nikolakopoulou, Deric M Park, Alan Mcintyre, Mathias Lesche, Andreas Dahl, Petra Lennig, Stefan R. Bornstein, Evelin Schroeck, Barbara Klink, Ronen R Leker, Marc Bickle, George P Chrousos, Michael Schroeder, Carlo Vittorio Cannistraci, Jochen Guck, Andreas Androutsellis-Theotokis
Controlling distinct signaling states in cultured cancer cells provides a new platform for drug discovery.
FASEB J, Art. No. doi: 10.1096/fj.201802603RR (2019)
PubMed Source   

Cancer cells can switch between signaling pathways to regulate growth under different conditions. In the tumor microenvironment, this likely helps them evade therapies that target specific pathways. We must identify all possible states and utilize them in drug screening programs. One such state is characterized by expression of the transcription factor Hairy and Enhancer of Split 3 (HES3) and sensitivity to HES3 knockdown, and it can be modeled in vitro. Here, we cultured 3 primary human brain cancer cell lines under 3 different culture conditions that maintain low, medium, and high HES3 expression and characterized gene regulation and mechanical phenotype in these states. We assessed gene expression regulation following HES3 knockdown in the HES3-high conditions. We then employed a commonly used human brain tumor cell line to screen Food and Drug Administration (FDA)-approved compounds that specifically target the HES3-high state. We report that cells from multiple patients behave similarly when placed under distinct culture conditions. We identified 37 FDA-approved compounds that specifically kill cancer cells in the high-HES3-expression conditions. Our work reveals a novel signaling state in cancer, biomarkers, a strategy to identify treatments against it, and a set of putative drugs for potential repurposing.-Poser, S. W., Otto, O., Arps-Forker, C., Ge, Y., Herbig, M., Andree, C., Gruetzmann, K., Adasme, M. F., Stodolak, S., Nikolakopoulou, P., Park, D. M., Mcintyre, A., Lesche, M., Dahl, A., Lennig, P., Bornstein, S. R., Schroeck, E., Klink, B., Leker, R. R., Bickle, M., Chrousos, G. P., Schroeder, M., Cannistraci, C. V., Guck, J., Androutsellis-Theotokis, A. Controlling distinct signaling states in cultured cancer cells provides a new platform for drug discovery.
@article{Poser7403,
author={Steven W Poser, Oliver Otto, Carina Arps-Forker, Yan Ge, Maik Herbig, Cordula Andree, Konrad Gruetzmann, Melissa F Adasme, Szymon Stodolak, Polyxeni Nikolakopoulou, Deric M Park, Alan Mcintyre, Mathias Lesche, Andreas Dahl, Petra Lennig, Stefan R. Bornstein, Evelin Schroeck, Barbara Klink, Ronen R Leker, Marc Bickle, George P Chrousos, Michael Schroeder, Carlo Vittorio Cannistraci, Jochen Guck, Andreas Androutsellis-Theotokis},
title={Controlling distinct signaling states in cultured cancer cells provides a new platform for drug discovery.},
journal ={FASEB journal : official publication of the Federation of American Societies for Experimental Biology},
volume={},
pages={null--null},
year=2019
}

Mareike A Jordan, Gaia Pigino
In situ cryo-electron tomography and subtomogram averaging of intraflagellar transport trains
Methods Cell Biol, Art. No. doi: 10.1016/bs.mcb.2019.04.005 (2019)
Source  

@article{Jordan7409,
author={Mareike A Jordan, Gaia Pigino},
title={In situ cryo-electron tomography and subtomogram averaging of intraflagellar transport trains},
journal ={Methods in cell biology},
volume={},
pages={1--1},
year=2019
}

Rana Amini, Anastasia Labudina, Caren Norden
Stochastic single cell migration leads to robust horizontal cell layer formation in the vertebrate retina.
Development, 146(12) Art. No. dev173450 (2019)
PubMed Source   

Developmental programs that arrange cells and tissues into patterned organs are remarkably robust. In the developing vertebrate retina, for example, neurons reproducibly assemble into distinct layers giving the mature organ its overall structured appearance. This stereotypic neuronal arrangement, termed lamination, is important for efficient neuronal connectivity. Although retinal lamination is conserved in many vertebrates, including humans, how it emerges from single cell behaviour is not fully understood. To shed light on this issue, we here investigated the formation of the retinal horizontal cell layer. Using in vivo light sheet imaging of the developing zebrafish retina, we generated a comprehensive quantitative analysis of horizontal single cell behaviour from birth to final positioning. Interestingly, we find that all parameters analysed, including cell cycle dynamics, migration paths and kinetics, as well as sister cell dispersal, are very heterogeneous. Thus, horizontal cells show individual non-stereotypic behaviour before final positioning. Yet these initially variable cell dynamics always generate the correct laminar pattern. Consequently, our data show that the extent of single cell stochasticity in the lamination of the vertebrate retina is underexplored.
@article{Amini7396,
author={Rana Amini, Anastasia Labudina, Caren Norden},
title={Stochastic single cell migration leads to robust horizontal cell layer formation in the vertebrate retina.},
journal ={Development (Cambridge, England)},
volume={146},
issue ={12},
pages={null--null},
year=2019
}

Branislav Krljanac, Christoph Schubart, Ronald Naumann, Stefan Wirtz, Stephan Culemann, Gerhard Krönke, David Voehringer
RELMα-expressing macrophages protect against fatal lung damage and reduce parasite burden during helminth infection.
Sci Immunol, 4(35) Art. No. eaau3814 (2019)
PubMed Source   

Alternatively activated macrophages (AAMs) can contribute to wound healing, regulation of glucose and fat metabolism, resolution of inflammation, and protective immunity against helminths. Their differentiation, tissue distribution, and effector functions are incompletely understood. Murine AAMs express high levels of resistin-like molecule (RELM) α, an effector protein with potent immunomodulatory functions. To visualize RELMα+ macrophages (MΦs) in vivo and evaluate their role in defense against helminths, we generated RELMα reporter/deleter mice. Infection with the helminth Nippostrongylus brasiliensis induced expansion of RELMα+ lung interstitial but not alveolar MΦs in a STAT6-dependent manner. RELMα+ MΦs were required for prevention of fatal lung damage during primary infection. Furthermore, protective immunity was lost upon specific deletion of RELMα+ MΦs during secondary infection. Thus, RELMα reporter/deleter mice reveal compartmentalization of AAMs in different tissues and demonstrate their critical role in resolution of severe lung inflammation and protection against migrating helminths.
@article{Krljanac7397,
author={Branislav Krljanac, Christoph Schubart, Ronald Naumann, Stefan Wirtz, Stephan Culemann, Gerhard Krönke, David Voehringer},
title={RELMα-expressing macrophages protect against fatal lung damage and reduce parasite burden during helminth infection.},
journal ={Science immunology},
volume={4},
issue ={35},
pages={null--null},
year=2019
}