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Developmental Cell

Wei Song, Serkan Kir, Shangyu Hong, Yanhui Hu, Xiaohui Wang, Richard Binari, Hong-Wen Tang, Verena Chung, Alexander S Banks, Bruce Spiegelman, Norbert Perrimon
Interactions between tumors and host tissues play essential roles in tumor-induced systemic wasting and cancer cachexia, including muscle wasting and lipid loss. However, the pathogenic molecular mechanisms of wasting are still poorly understood. Using a fly model of tumor-induced organ wasting, we observed aberrant MEK activation in both tumors and host tissues of flies bearing gut-yki3SA tumors. We found that host MEK activation results in muscle wasting and lipid loss, while tumor MEK activation is required for tumor growth...
January 2, 2019: Developmental Cell
Hisamichi Naito, Tomohiro Iba, Taku Wakabayashi, Ikue Tai-Nagara, Jun-Ichi Suehiro, Weizhen Jia, Daisuke Eino, Susumu Sakimoto, Fumitaka Muramatsu, Hiroyasu Kidoya, Hiroyuki Sakurai, Takashi Satoh, Shizuo Akira, Yoshiaki Kubota, Nobuyuki Takakura
TNF-α is a pleiotropic cytokine that has the potential to induce apoptosis under inflammation. How endothelial cells (ECs) are spared from this fate in inflammatory environments where TNF-α is present is not known. Here, we show that TGF-β-activated kinase 1 (TAK1) ensures EC survival and maintains vascular integrity upon TNF-α stimulation. Endothelial-specific TAK1 knockout mice exhibit intestinal and liver hemorrhage due to EC apoptosis, leading to vascular destruction and rapid death. This EC apoptosis was induced by TNF-α from myeloid cells responding to intestinal microbiota...
December 31, 2018: Developmental Cell
John M E Nichols, Peggy Paschke, Sew Peak-Chew, Thomas D Williams, Luke Tweedy, Mark Skehel, Elaine Stephens, Jonathan R Chubb, Robert R Kay
Signaling from chemoattractant receptors activates the cytoskeleton of crawling cells for chemotaxis. We show using phosphoproteomics that different chemoattractants cause phosphorylation of the same core set of around 80 proteins in Dictyostelium cells. Strikingly, the majority of these are phosphorylated at an [S/T]PR motif by the atypical MAP kinase ErkB. Unlike most chemotactic responses, ErkB phosphorylations are persistent and do not adapt to sustained stimulation with chemoattractant. ErkB integrates dynamic autophosphorylation with chemotactic signaling through G-protein-coupled receptors...
December 31, 2018: Developmental Cell
Weimin Zhang, Xuedi Zhang, Zhaoyu Xue, Yijie Li, Qing Ma, Xiangle Ren, Jiaying Zhang, Songhua Yang, Lijuan Yang, Menghua Wu, Mengda Ren, Rongwen Xi, Zheng Wu, Ji-Long Liu, Erika Matunis, Junbiao Dai, Guanjun Gao
Replication-dependent histone genes often reside in tandemly arrayed gene clusters, hindering systematic loss-of-function analyses. Here, we used CRISPR/Cas9 and the attP/attB double-integration system to alter numbers and sequences of histone genes in their original genomic context in Drosophila melanogaster. As few as 8 copies of the histone gene unit supported embryo development and adult viability, whereas flies with 20 copies were indistinguishable from wild-types. By hierarchical assembly, 40 alanine-substitution mutations (covering all known modified residues in histones H3 and H4) were introduced and characterized...
December 27, 2018: Developmental Cell
Xinbo Wang, Jiali Jin, Fangning Wan, Linlin Zhao, Hongshang Chu, Cong Chen, Guanghong Liao, Jian Liu, Yue Yu, Hongqi Teng, Lan Fang, Cong Jiang, Weijuan Pan, Xin Xie, Jia Li, Xiaolin Lu, Xuejun Jiang, Xin Ge, Dingwei Ye, Ping Wang
NANOG is an essential transcriptional factor for the maintenance of embryonic stem cells (ESCs) and cancer stem cells (CSCs) in prostate cancer (PCa). However, the regulation mechanism of NANOG protein stability in cancer progression is still elusive. Here, we report that NANOG is degraded by SPOP, a frequently mutated tumor suppressor of PCa. Cancer-associated mutations of SPOP or the mutation of NANOG at S68Y abrogates the SPOP-mediated NANOG degradation, leading to elevated PCa cancer stemness and poor prognosis...
December 21, 2018: Developmental Cell
Jinfang Zhang, Ming Chen, Yasheng Zhu, Xiangpeng Dai, Fabin Dang, Junming Ren, Shancheng Ren, Yulia V Shulga, Francisco Beca, Wenjian Gan, Fei Wu, Yu-Min Lin, Xiaobo Zhou, James A DeCaprio, Andrew H Beck, Kun Ping Lu, Jiaoti Huang, Cheryl Zhao, Yinghao Sun, Xu Gao, Pier Paolo Pandolfi, Wenyi Wei
Frequent SPOP mutation defines the molecular feature underlying one of seven sub-types of human prostate cancer (PrCa). However, it remains largely elusive how SPOP functions as a tumor suppressor in PrCa. Here, we report that SPOP suppresses stem cell traits of both embryonic stem cells and PrCa cells through promoting Nanog poly-ubiquitination and subsequent degradation. Mechanistically, Nanog, but not other pluripotency-determining factors including Oct4, Sox2, and Klf4, specifically interacts with SPOP via a conservative degron motif...
December 20, 2018: Developmental Cell
Ka-Wai Mok, Nivedita Saxena, Nicholas Heitman, Laura Grisanti, Devika Srivastava, Mauro J Muraro, Tina Jacob, Rachel Sennett, Zichen Wang, Yutao Su, Lu M Yang, Avi Ma'ayan, David M Ornitz, Maria Kasper, Michael Rendl
Cell fate transitions are essential for specification of stem cells and their niches, but the precise timing and sequence of molecular events during embryonic development are largely unknown. Here, we identify, with 3D and 4D microscopy, unclustered precursors of dermal condensates (DC), signaling niches for epithelial progenitors in hair placodes. With population-based and single-cell transcriptomics, we define a molecular time-lapse from pre-DC fate specification through DC niche formation and establish the developmental trajectory as the DC lineage emerges from fibroblasts...
December 20, 2018: Developmental Cell
Xiaofeng Fang, Gaozhan Zhao, Su Zhang, Yaoxi Li, Hanqing Gu, Yan Li, Qiao Zhao, Yijun Qi
As integral regulators in plant development and stress response, microRNAs (miRNAs) themselves need to be tightly regulated. Here, we show that tocopherols (vitamin E), lipid-soluble antioxidants synthesized from tyrosine in chloroplasts, positively regulate the biogenesis of miRNAs. Tocopherols are required for the accumulation of 3'-phosphoadenosine 5'-phosphate (PAP), a retrograde inhibitor of the nuclear exoribonucleases (XRN), which may protect primary miRNAs from being degraded and promote mature miRNA production...
December 20, 2018: Developmental Cell
Khusali Gupta, Jonathan Levinsohn, George Linderman, Demeng Chen, Thomas Yang Sun, Danni Dong, M Mark Taketo, Marcus Bosenberg, Yuval Kluger, Keith Choate, Peggy Myung
Delineating molecular and cellular events that precede appendage morphogenesis has been challenging due to the inability to distinguish quantitative molecular differences between cells that lack histological distinction. The hair follicle (HF) dermal condensate (DC) is a cluster of cells critical for HF development and regeneration. Events that presage emergence of this distinctive population are poorly understood. Using unbiased single-cell RNA sequencing and in vivo methods, we infer a sequence of transcriptional states through which DC cells pass that begins prior to HF morphogenesis...
December 19, 2018: Developmental Cell
Koichi Toyokura, Tatsuaki Goh, Hidefumi Shinohara, Akinori Shinoda, Yuki Kondo, Yoshie Okamoto, Takeo Uehara, Koichi Fujimoto, Yoko Okushima, Yoshifumi Ikeyama, Keiji Nakajima, Tetsuro Mimura, Masao Tasaka, Yoshikatsu Matsubayashi, Hidehiro Fukaki
In plants, the position of lateral roots (LRs) depends on initiation sites induced by auxin. The domain of high auxin response responsible for LR initiation stretches over several cells, but only a pair of pericycle cells (LR founder cells) will develop into LRs. In this work, we identified a signaling cascade controlling LR formation through lateral inhibition. It comprises a peptide hormone TARGET OF LBD SIXTEEN 2 (TOLS2), its receptor RLK7, and a downstream transcription factor PUCHI. TOLS2 is expressed at the LR founder cells and inhibits LR initiation...
December 17, 2018: Developmental Cell
Eleonora Meschi, Pierre Léopold, Renald Delanoue
Developing organisms use fine-tuning mechanisms to adjust body growth to ever-changing nutritional conditions. In Drosophila, the secretory activity of insulin-producing cells (IPCs) is central to couple systemic growth with amino acids availability. Here, we identify a subpopulation of inhibitory neurons contacting the IPCs (IPC-connecting neurons or ICNs) that play a key role in this coupling. We show that ICNs respond to growth-blocking peptides (GBPs), a family of fat-body-derived signals produced upon availability of dietary amino acids...
December 10, 2018: Developmental Cell
Edith Francoz, Philippe Ranocha, Aurélie Le Ru, Yves Martinez, Isabelle Fourquaux, Alain Jauneau, Christophe Dunand, Vincent Burlat
Plant cell walls are made of polysaccharidic-proteinaceous complex matrices. Molecular interactions governing their organization remain understudied. We take advantage of the highly dynamic cell walls of Arabidopsis seed mucilage secretory cells to propose a hierarchical multi-molecular interaction model within a cell wall domain. We show that the PECTINMETHYLESTERASE INHIBITOR6 activity creates a partially demethylesterified pectin pattern acting as a platform allowing positioning of PEROXIDASE36 in a remote primary cell wall domain during early development...
December 10, 2018: Developmental Cell
Chun-Hao Chen, Hao-Wei Hsu, Yun-Hsuan Chang, Chun-Liang Pan
Neurite fasciculation through contact-dependent signaling is important for the wiring and function of the neuronal circuits. Here, we describe a type of axon-dendrite fasciculation in C. elegans, where proximal dendrites of the nociceptor PVD adhere to the axon of the ALA interneuron. This axon-dendrite fasciculation is mediated by a previously uncharacterized adhesive signaling by the ALA membrane signal SAX-7/L1CAM and the PVD receptor SAX-3/Robo but independent of Slit. L1CAM physically interacts with Robo and instructs dendrite adhesion in a Robo-dependent manner...
December 10, 2018: Developmental Cell
Gilles Storelli, Hyuck-Jin Nam, Judith Simcox, Claudio J Villanueva, Carl S Thummel
Animals must adjust their metabolism as they progress through development in order to meet the needs of each stage in the life cycle. Here, we show that the dHNF4 nuclear receptor acts at the onset of Drosophila adulthood to direct an essential switch in lipid metabolism. Lipid stores are consumed shortly after metamorphosis but contribute little to energy metabolism. Rather, dHNF4 directs their conversion to very long chain fatty acids and hydrocarbons, which waterproof the animal to preserve fluid homeostasis...
December 10, 2018: Developmental Cell
Wen-Chi Yin, Thevagi Satkunendran, Rong Mo, Sorana Morrissy, Xiaoyun Zhang, Eunice Shiao Huang, Liis Uusküla-Reimand, Huayun Hou, Joe Eun Son, Weifan Liu, Yulu C Liu, Jianing Zhang, Jessica Parker, Xin Wang, Hamza Farooq, Hayden Selvadurai, Xin Chen, Elly Sau-Wai Ngan, Steven Y Cheng, Peter B Dirks, Stephane Angers, Michael D Wilson, Michael D Taylor, Chi-Chung Hui
SUFU alterations are common in human Sonic Hedgehog (SHH) subgroup medulloblastoma (MB). However, its tumorigenic mechanisms have remained elusive. Here, we report that loss of Sufu alone is unable to induce MB formation in mice, due to insufficient Gli2 activation. Simultaneous loss of Spop, an E3 ubiquitin ligase targeting Gli2, restores robust Gli2 activation and induces rapid MB formation in Sufu knockout background. We also demonstrated a tumor-promoting role of Sufu in Smo-activated MB (∼60% of human SHH MB) by maintaining robust Gli activity...
December 7, 2018: Developmental Cell
Laura L Thomas, Solveig A van der Vegt, J Christopher Fromme
Correct localization of Rab GTPases in cells is critical for proper function in membrane trafficking, yet the mechanisms that target Rabs to specific subcellular compartments remain controversial. Guanine nucleotide exchange factors (GEFs) activate and consequently stabilize Rab substrates on membranes, thus implicating GEFs as the primary determinants of Rab localization. A competing hypothesis is that the Rab C-terminal hypervariable domain (HVD) serves as a subcellular targeting signal. In this study, we present a unifying mechanism in which the HVD controls targeting of certain Rabs by mediating interaction with their GEFs...
December 3, 2018: Developmental Cell
Sabrina Förster, Lena K Schmidt, Eva Kopic, Uta Anschütz, Shouguang Huang, Kathrin Schlücking, Philipp Köster, Rainer Waadt, Antoine Larrieu, Oliver Batistič, Pedro L Rodriguez, Erwin Grill, Jörg Kudla, Dirk Becker
Guard cells integrate various hormone signals and environmental cues to balance plant gas exchange and transpiration. The wounding-associated hormone jasmonic acid (JA) and the drought hormone abscisic acid (ABA) both trigger stomatal closure. In contrast to ABA however, the molecular mechanisms of JA-induced stomatal closure have remained largely elusive. Here, we identify a fast signaling pathway for JA targeting the K+ efflux channel GORK. Wounding triggers both local and systemic stomatal closure by activation of the JA signaling cascade followed by GORK phosphorylation and activation through CBL1-CIPK5 Ca2+ sensor-kinase complexes...
December 3, 2018: Developmental Cell
Elena Scarpa, Cédric Finet, Guy B Blanchard, Bénédicte Sanson
Cell shape is known to influence the plane of cell division. In vitro, mechanical constraints can also orient mitoses; however, in vivo it is not clear whether tension can orient the mitotic spindle directly, because tissue-scale forces can change cell shape. During segmentation of the Drosophila embryo, actomyosin is enriched along compartment boundaries forming supracellular cables that keep cells segregated into distinct compartments. Here, we show that these actomyosin cables orient the planar division of boundary cells perpendicular to the boundaries...
November 26, 2018: Developmental Cell
Christoph Schell, Benedikt Sabass, Martin Helmstaedter, Felix Geist, Ahmed Abed, Mako Yasuda-Yamahara, August Sigle, Jasmin I Maier, Florian Grahammer, Florian Siegerist, Nadine Artelt, Nicole Endlich, Dontscho Kerjaschki, Hans-Henning Arnold, Jörn Dengjel, Manuel Rogg, Tobias B Huber
Podocytes, highly specialized epithelial cells, build the outer part of the kidney filtration barrier and withstand high mechanical forces through a complex network of cellular protrusions. Here, we show that Arp2/3-dependent actin polymerization controls actomyosin contractility and focal adhesion maturation of podocyte protrusions and thereby regulates formation, maintenance, and capacity to adapt to mechanical requirements of the filtration barrier. We find that N-WASP-Arp2/3 define the development of complex arborized podocyte protrusions in vitro and in vivo...
November 26, 2018: Developmental Cell
Lydia Farack, Matan Golan, Adi Egozi, Nili Dezorella, Keren Bahar Halpern, Shani Ben-Moshe, Immacolata Garzilli, Beáta Tóth, Lior Roitman, Valery Krizhanovsky, Shalev Itzkovitz
Pancreatic beta cells have been shown to be heterogeneous at multiple levels. However, spatially interrogating transcriptional heterogeneity in the intact tissue has been challenging. Here, we developed an optimized protocol for single-molecule transcript imaging in the intact pancreas and used it to identify a sub-population of "extreme" beta cells with elevated mRNA levels of insulin and other secretory genes. Extreme beta cells contain higher ribosomal and proinsulin content but lower levels of insulin protein in fasted states, suggesting they may be tuned for basal insulin secretion...
November 22, 2018: Developmental Cell
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