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Developmental Cell

Fred Etoc, Jakob Metzger, Albert Ruzo, Christoph Kirst, Anna Yoney, M Zeeshan Ozair, Ali H Brivanlou, Eric D Siggia
The earliest aspects of human embryogenesis remain mysterious. To model patterning events in the human embryo, we used colonies of human embryonic stem cells (hESCs) grown on micropatterned substrate and differentiated with BMP4. These gastruloids recapitulate the embryonic arrangement of the mammalian germ layers and provide an assay to assess the structural and signaling mechanisms patterning the human gastrula. Structurally, high-density hESCs localize their receptors to transforming growth factor β at their lateral side in the center of the colony while maintaining apical localization of receptors at the edge...
October 13, 2016: Developmental Cell
Arnau Sebé-Pedrós, Marcia Ivonne Peña, Salvador Capella-Gutiérrez, Meritxell Antó, Toni Gabaldón, Iñaki Ruiz-Trillo, Eduard Sabidó
Cell-specific regulation of protein levels and activity is essential for the distribution of functions among multiple cell types in animals. The finding that many genes involved in these regulatory processes have a premetazoan origin raises the intriguing possibility that the mechanisms required for spatially regulated cell differentiation evolved prior to the appearance of animals. Here, we use high-throughput proteomics in Capsaspora owczarzaki, a close unicellular relative of animals, to characterize the dynamic proteome and phosphoproteome profiles of three temporally distinct cell types in this premetazoan species...
October 8, 2016: Developmental Cell
Jyoti R Misra, Kenneth D Irvine
The protocadherins Dachsous and Fat initiate a signaling pathway that controls growth and planar cell polarity by regulating the membrane localization of the atypical myosin Dachs. How Dachs is regulated by Fat signaling has remained unclear. Here we identify the vamana gene as playing a crucial role in regulating membrane localization of Dachs and in linking Fat and Dachsous to Dachs regulation. Vamana, an SH3-domain-containing protein, physically associates with and co-localizes with Dachs and promotes its membrane localization...
October 7, 2016: Developmental Cell
Cornelia Habacher, Yanwu Guo, Richard Venz, Pooja Kumari, Anca Neagu, Dimos Gaidatzis, Eva B Harvald, Nils J Færgeman, Heinz Gut, Rafal Ciosk
Obesity is a global health issue, arousing interest in molecular mechanisms controlling fat. Transcriptional regulation of fat has received much attention, and key transcription factors involved in lipid metabolism, such as SBP-1/SREBP, LPD-2/C/EBP, and MDT-15, are conserved from nematodes to mammals. However, there is a growing awareness that lipid metabolism can also be controlled by post-transcriptional mechanisms. Here, we show that the Caenorhabditis elegans RNase, REGE-1, related to MCPIP1/Zc3h12a/Regnase-1, a key regulator of mammalian innate immunity, promotes accumulation of body fat...
October 7, 2016: Developmental Cell
Guoqiang Ma, Shuang Li, Yuhong Han, Shuangxi Li, Tao Yue, Bing Wang, Jin Jiang
Hedgehog (Hh) signaling plays a central role in development and diseases. Hh activates its signal transducer and GPCR-family protein Smoothened (Smo) by inducing Smo phosphorylation, but whether Smo is activated through other post-translational modifications remains unexplored. Here we show that sumoylation acts in parallel with phosphorylation to promote Smo cell-surface expression and Hh signaling. We find that Hh stimulates Smo sumoylation by dissociating it from a desumoylation enzyme Ulp1. Sumoylation of Smo in turn recruits a deubiquitinase UBPY/USP8 to antagonize Smo ubiquitination and degradation, leading to its cell-surface accumulation and elevated Hh pathway activity...
October 7, 2016: Developmental Cell
Kotaro Sasaki, Tomonori Nakamura, Ikuhiro Okamoto, Yukihiro Yabuta, Chizuru Iwatani, Hideaki Tsuchiya, Yasunari Seita, Shinichiro Nakamura, Naoto Shiraki, Tetsuya Takakuwa, Takuya Yamamoto, Mitinori Saitou
The germ cell lineage ensures reproduction and heredity. The mechanism for germ cell specification in primates, including humans, has remained unknown. In primates, upon implantation the pluripotent epiblast segregates the amnion, an extra-embryonic membrane eventually ensheathing an embryo, and thereafter initiates gastrulation to generate three germ layers. Here, we show that in cynomolgus monkeys, the SOX17/TFAP2C/BLIMP1-positive primordial germ cells (cyPGCs) originate from the dorsal amnion at embryonic day 11 (E11) prior to gastrulation...
October 6, 2016: Developmental Cell
Yen-Chih Chen, Hung-Jhen Chen, Wei-Chin Tseng, Jiun-Min Hsu, Tzu-Ting Huang, Chun-Hao Chen, Chun-Liang Pan
Sensory perception, including thermosensation, shapes longevity in diverse organisms, but longevity-modulating signals from the sensory neurons are largely obscure. Here we show that CRH-1/CREB activation by CMK-1/CaMKI in the AFD thermosensory neuron is a key mechanism that maintains lifespan at warm temperatures in C. elegans. In response to temperature rise and crh-1 activation, the AFD neurons produce and secrete the FMRFamide neuropeptide FLP-6. Both CRH-1 and FLP-6 are necessary and sufficient for longevity at warm temperatures...
October 5, 2016: Developmental Cell
Timothy E Audas, Danielle E Audas, Mathieu D Jacob, J J David Ho, Mireille Khacho, Miling Wang, J Kishan Perera, Caroline Gardiner, Clay A Bennett, Trajen Head, Oleksandr N Kryvenko, Mercé Jorda, Sylvia Daunert, Arun Malhotra, Laura Trinkle-Mulcahy, Mark L Gonzalgo, Stephen Lee
The amyloid state of protein organization is typically associated with debilitating human neuropathies and is seldom observed in physiology. Here, we uncover a systemic program that leverages the amyloidogenic propensity of proteins to regulate cell adaptation to stressors. On stimulus, cells assemble the amyloid bodies (A-bodies), nuclear foci containing heterogeneous proteins with amyloid-like biophysical properties. A discrete peptidic sequence, termed the amyloid-converting motif (ACM), is capable of targeting proteins to the A-bodies by interacting with ribosomal intergenic noncoding RNA (rIGSRNA)...
October 4, 2016: Developmental Cell
Teemu P Miettinen, Mikael Björklund
Eukaryotic cells attempt to maintain an optimal size, resulting in size homeostasis. While cellular content scales isometrically with cell size, allometric laws indicate that metabolism per mass unit should decline with increasing size. Here we use elutriation and single-cell flow cytometry to analyze mitochondrial scaling with cell size. While mitochondrial content increases linearly, mitochondrial membrane potential and oxidative phosphorylation are highest at intermediate cell sizes. Thus, mitochondrial content and functional scaling are uncoupled...
October 4, 2016: Developmental Cell
Timo H Lüdtke, Carsten Rudat, Irina Wojahn, Anna-Carina Weiss, Marc-Jens Kleppa, Jennifer Kurz, Henner F Farin, Anne Moon, Vincent M Christoffels, Andreas Kispert
Numerous signals drive the proliferative expansion of the distal endoderm and the underlying mesenchyme during lung branching morphogenesis, but little is known about how these signals are integrated. Here, we show by analysis of conditional double mutants that the two T-box transcription factor genes Tbx2 and Tbx3 act together in the lung mesenchyme to maintain branching morphogenesis. Expression of both genes depends on epithelially derived Shh signaling, with additional modulation by Bmp, Wnt, and Tgfβ signaling...
October 4, 2016: Developmental Cell
Zhiqiang Lin, Haidong Guo, Yuan Cao, Sylvia Zohrabian, Pingzhu Zhou, Qing Ma, Nathan VanDusen, Yuxuan Guo, Jin Zhang, Sean M Stevens, Feng Liang, Qimin Quan, Pim R van Gorp, Amy Li, Cristobal Dos Remedios, Aibin He, Vassilios J Bezzerides, William T Pu
Binding of the transcriptional co-activator YAP with the transcription factor TEAD stimulates growth of the heart and other organs. YAP overexpression potently stimulates fetal cardiomyocyte (CM) proliferation, but YAP's mitogenic potency declines postnatally. While investigating factors that limit YAP's postnatal mitogenic activity, we found that the CM-enriched TEAD1 binding protein VGLL4 inhibits CM proliferation by inhibiting TEAD1-YAP interaction and by targeting TEAD1 for degradation. Importantly, VGLL4 acetylation at lysine 225 negatively regulated its binding to TEAD1...
October 4, 2016: Developmental Cell
Stefano Bencivenga, Antonio Serrano-Mislata, Max Bush, Samantha Fox, Robert Sablowski
The origin of the stem is a major but poorly understood aspect of plant development, partly because the stem initiates in a relatively inaccessible region of the shoot apical meristem called the rib zone (RZ). We developed quantitative 3D image analysis and clonal analysis tools, which revealed that the Arabidopsis homeodomain protein REPLUMLESS (RPL) establishes distinct patterns of oriented cell division and growth in the central and peripheral regions of the RZ. A genome-wide screen for target genes connected RPL directly to many of the key shoot development pathways, including the development of organ boundaries; accordingly, mutation of the organ boundary gene LIGHT-SENSITIVE HYPOCOTYL 4 restored RZ function and stem growth in the rpl mutant...
September 14, 2016: Developmental Cell
Heather J Kolpa, Frank O Fackelmayer, Jeanne B Lawrence
No abstract text is available yet for this article.
October 10, 2016: Developmental Cell
Florian Hoss, Christina F Budden, Eicke Latz
When bacteria infect a cell, the bacterial membrane partially shields microbial structures from the immune system, preventing detection and clearance. In a recent issue of Cell, Man et al. (2016) show that the interferon-inducible protein IRGB10 liberates bacterial ligands for sensing by both the AIM2 and the non-canonical NLRP3 inflammasomes.
October 10, 2016: Developmental Cell
Sanna Koskiniemi, Johan Elf
Bacteria use type 6 secretion systems in antagonistic behavior to compete for resources with other bacteria. In a recent issue of Cell, Vettiger and Basler (2016) show that bacteria can also use these systems to arm neighboring cells and force them to pass on a signal in the bacterial population.
October 10, 2016: Developmental Cell
David J McGarry, Michael F Olson
Unravelling the role of cytoskeleton regulators may be complicated by adaptations to experimental manipulations. In this issue of Developmental Cell, Cerikan et al. (2016) reveal how acute effects of DOCK6 RhoGEF depletion on RAC1 and CDC42 activation are reversed over time by compensatory mechanisms that re-establish cellular homeostasis.
October 10, 2016: Developmental Cell
Takehisa Sakaguchi, Yuko Hasegawa, Neil Brockdorff, Ken Tsutsui, Kimiko M Tsutsui, Takashi Sado, Shinichi Nakagawa
No abstract text is available yet for this article.
October 10, 2016: Developmental Cell
Ferdinand von Meyenn, Rebecca V Berrens, Simon Andrews, Fátima Santos, Amanda J Collier, Felix Krueger, Rodrigo Osorno, Wendy Dean, Peter J Rugg-Gunn, Wolf Reik
Primordial germ cell (PGC) development is characterized by global epigenetic remodeling, which resets genomic potential and establishes an epigenetic ground state. Here we recapitulate PGC specification in vitro from naive embryonic stem cells and characterize the early events of epigenetic reprogramming during the formation of the human and mouse germline. Following rapid de novo DNA methylation during priming to epiblast-like cells, methylation is globally erased in PGC-like cells. Repressive chromatin marks (H3K9me2/3) and transposable elements are enriched at demethylation-resistant regions, while active chromatin marks (H3K4me3 or H3K27ac) are more prominent at regions that demethylate faster...
October 10, 2016: Developmental Cell
Milana Fraiberg, Zvulun Elazar
Selective autophagy, an essential process for maintaining intracellular homeostasis, depends on precise target recognition and local activation. Reporting in Developmental Cell, Chauhan et al. (2016) elegantly demonstrate that interaction between TRIM16 and Galectin3 orchestrates the recruitment of core autophagic factors and activates selective autophagy at the site of damaged endomembranes.
October 10, 2016: Developmental Cell
Wenxiu Ning, Yanan Yu, Honglin Xu, Xiaofei Liu, Daiwei Wang, Jing Wang, Yingchun Wang, Wenxiang Meng
For adaptation to complex cellular functions, dynamic cytoskeletal networks are required. There are two major components of the cytoskeleton, microtubules and actin filaments, which form an intricate network maintaining an exquisite cooperation to build the physical basis for their cellular function. However, little is known about the molecular mechanism underlying their synergism. Here, we show that in Caco2 epithelial cells, noncentrosomal microtubules crosstalk with F-actin through their minus ends and contribute to the regulation of focal adhesion size and cell migration...
October 10, 2016: Developmental Cell
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