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Developmental Cell

Xiying Fan, Dongmei Wang, Jeremy Evan Burgmaier, Yudong Teng, Rose-Anne Romano, Satrajit Sinha, Rui Yi
How embryonic progenitors coordinate cell fate specification and establish transcriptional and signaling competence is a fundamental question in developmental biology. Here, we show that transcription factor ΔNp63 profoundly changes the transcriptome and remodels thousands of open chromatin regions of Krt8+ progenitors during epidermal fate specification. ATAC-seq and single-cell RNA-seq reveal that ΔNp63-dependent programs govern epidermal lineage formation, and ΔNp63-independent programs, mediated by AP2 and AP1 transcription factors, promote epidermal differentiation and epithelial-to-mesenchymal transition...
September 13, 2018: Developmental Cell
Rebecca Obniski, Matthew Sieber, Allan C Spradling
Tissue homeostasis involves a complex balance of developmental signals and environmental cues that dictate stem cell function. We found that dietary lipids control enteroendocrine cell production from Drosophila posterior midgut stem cells. Dietary cholesterol influences new intestinal cell differentiation in an Hr96-dependent manner by altering the level and duration of Notch signaling. Exogenous lipids modulate Delta ligand and Notch extracellular domain stability and alter their trafficking in endosomal vesicles...
September 12, 2018: Developmental Cell
Lena M Kutscher, Wolfgang Keil, Shai Shaham
Clearance of dying cells is essential for development and homeostasis. Conserved genes mediate apoptotic cell removal, but whether these genes control non-apoptotic cell removal is a major open question. Linker cell-type death (LCD) is a prevalent non-apoptotic developmental cell death process with features conserved from C. elegans to vertebrates. Using microfluidics-based long-term in vivo imaging, we show that unlike apoptotic cells, the C. elegans linker cell, which dies by LCD, is competitively phagocytosed by two neighboring cells, resulting in cell splitting...
September 7, 2018: Developmental Cell
Jaakko Mattila, Krista Kokki, Ville Hietakangas, Michael Boutros
The intestine is an organ with an exceptionally high rate of cell turnover, and perturbations in this process can lead to severe diseases such as cancer or intestinal atrophy. Nutrition has a profound impact on intestinal volume and cellular architecture. However, how intestinal homeostasis is maintained in fluctuating dietary conditions remains insufficiently understood. By utilizing the Drosophila midgut model, we reveal a novel stem cell intrinsic mechanism coupling cellular metabolism with stem cell extrinsic growth signal...
September 7, 2018: Developmental Cell
Louise A Stephen, Yasmin ElMaghloob, Michael J McIlwraith, Tamas Yelland, Patricia Castro Sanchez, Pedro Roda-Navarro, Shehab Ismail
Upon engagement of the T cell receptor with an antigen-presenting cell, LCK initiates TCR signaling by phosphorylating its activation motifs. However, the mechanism of LCK activation specifically at the immune synapse is a major question. We show that phosphorylation of the LCK activating Y394, despite modestly increasing its catalytic rate, dramatically focuses LCK localization to the immune synapse. We describe a trafficking mechanism whereby UNC119A extracts membrane-bound LCK by sequestering the hydrophobic myristoyl group, followed by release at the target membrane under the control of the ciliary ARL3/ARL13B...
September 6, 2018: Developmental Cell
Tanu Singh, Eric H Lee, Tiffiney R Hartman, Dara M Ruiz-Whalen, Alana M O'Reilly
Egg production declines with age in many species, a process linked with stem cell loss. Diet-dependent signaling has emerged as critical for stem cell maintenance during aging. Follicle stem cells (FSCs) in the Drosophila ovary are exquisitely responsive to diet-induced signals including Hedgehog (Hh) and insulin-IGF signaling (IIS), entering quiescence in the absence of nutrients and initiating proliferation rapidly upon feeding. Although highly proliferative FSCs generally exhibit an extended lifespan, we find that constitutive Hh signaling drives FSC loss and premature sterility despite high proliferative rates...
September 4, 2018: Developmental Cell
Anne Vatén, Cara L Soyars, Paul T Tarr, Zachary L Nimchuk, Dominique C Bergmann
Coordinated growth of organs requires communication among cells within and between tissues. In plants, leaf growth is largely dictated by the epidermis; here, asymmetric and self-renewing divisions of the stomatal lineage create two essential cell types-pavement cells and guard cells-in proportions reflecting inputs from local, systemic, and environmental cues. The transcription factor SPEECHLESS (SPCH) is the prime regulator of divisions, but whether and how it is influenced by external cues to provide flexible development is enigmatic...
August 31, 2018: Developmental Cell
Evgenia Leikina, Dilani G Gamage, Vikram Prasad, Joanna Goykhberg, Michael Crowe, Jiajie Diao, Michael M Kozlov, Leonid V Chernomordik, Douglas P Millay
Classic mechanisms for membrane fusion involve transmembrane proteins that assemble into complexes and dynamically alter their conformation to bend membranes, leading to mixing of membrane lipids (hemifusion) and fusion pore formation. Myomaker and Myomerger govern myoblast fusion and muscle formation but are structurally divergent from traditional fusogenic proteins. Here, we show that Myomaker and Myomerger independently mediate distinct steps in the fusion pathway, where Myomaker is involved in membrane hemifusion and Myomerger is necessary for fusion pore formation...
August 30, 2018: Developmental Cell
Yuemin Celina Chee, Jens Pahnke, Ralph Bunte, Vikrant A Adsool, Babita Madan, David M Virshup
The gut absorbs dietary nutrients and provides a barrier to xenobiotics and microbiome metabolites. To cope with toxin exposures, the intestinal epithelium is one of the most rapidly proliferating tissues in the body. The stem cell niche supplies essential signaling factors including Wnt proteins secreted by subepithelial myofibroblasts. Unexpectedly, therapeutically effective doses of orally administered PORCN inhibitors that block all Wnt secretion do not affect intestinal homeostasis. We find that intestinal myofibroblasts are intrinsically resistant to multiple xenobiotics, including PORCN inhibitors and the anthracycline antibiotic doxorubicin...
August 21, 2018: Developmental Cell
Lale Alpar, Cora Bergantiños, Laura A Johnston
Cell competition employs comparisons of fitness to selectively eliminate cells sensed as less healthy. In Drosophila, apoptotic elimination of the weaker "loser" cells from growing wing discs is induced by a signaling module consisting of the Toll ligand Spätzle (Spz), several Toll-related receptors, and NF-κB factors. How this module is activated and restricted to competing disc cells is unknown. Here, we use Myc-induced cell competition to demonstrate that loser cell elimination requires local wing disc synthesis of Spz...
August 21, 2018: Developmental Cell
Yusuke Mochizuki, Tomoki Chiba, Kensuke Kataoka, Satoshi Yamashita, Tempei Sato, Tomomi Kato, Kenji Takahashi, Takeshi Miyamoto, Masashi Kitazawa, Tomohisa Hatta, Tohru Natsume, Shinro Takai, Hiroshi Asahara
SRY-box 9 (SOX9) is a master transcription factor that regulates cartilage development. SOX9 haploinsufficiency resulting from breakpoints in a ∼1-Mb region upstream of SOX9 was reported in acampomelic campomelic dysplasia (ACD) patients, suggesting that essential enhancer regions of SOX9 for cartilage development are located in this long non-coding sequence. However, the cis-acting enhancer region regulating cartilage-specific SOX9 expression remains to be identified. To identify distant cartilage Sox9 enhancers, we utilized the combination of multiple CRISPR/Cas9 technologies including enrichment of the promoter-enhancer complex followed by next-generation sequencing and mass spectrometry (MS), SIN3A-dCas9-mediated epigenetic silencing, and generation of enhancer deletion mice...
August 21, 2018: Developmental Cell
John Wang, Yandong Yin, Stephanie Lau, Jagadish Sankaran, Eli Rothenberg, Thorsten Wohland, Martin Meier-Schellersheim, Holger Knaut
Growth factors induce and pattern sensory organs, but how their distribution is regulated by the extracellular matrix (ECM) is largely unclear. To address this question, we analyzed the diffusion behavior of Fgf10 molecules during sensory organ formation in the zebrafish posterior lateral line primordium. In this tissue, secreted Fgf10 induces organ formation at a distance from its source. We find that most Fgf10 molecules are highly diffusive and move rapidly through the ECM. We identify Anosmin1, which when mutated in humans causes Kallmann Syndrome, as an ECM protein that binds to Fgf10 and facilitates its diffusivity by increasing the pool of fast-moving Fgf10 molecules...
August 14, 2018: Developmental Cell
Guifeng Wang, Hua Jiang, Gerardo Del Toro de León, German Martinez, Claudia Köhler
Genomic imprinting is an epigenetic phenomenon occurring in mammals and flowering plants, causing genes to be expressed depending on their parent of origin. In plants, genomic imprinting is mainly confined to the endosperm, a nutritive tissue supporting embryo growth, similar to the placenta in mammals. Here, we show that the paternally expressed imprinted gene PEG2 transcript sequesters the transposable element (TE)-derived small interfering RNA (siRNA) siRNA854 in the endosperm. siRNA854 is present in the vegetative cell of pollen and transferred to the central cell of the female gametophyte after fertilization, where it is captured by PEG2...
August 13, 2018: Developmental Cell
Saurabh S Kulkarni, John N Griffin, Priya P Date, Karel F Liem, Mustafa K Khokha
The actin cytoskeleton is critical to shape cells and pattern intracellular organelles, which collectively drives tissue morphogenesis. In multiciliated cells (MCCs), apical actin drives expansion of the cell surface necessary to host hundreds of cilia. The apical actin also forms a lattice to uniformly distribute basal bodies. This apical actin network is dynamically remodeled, but the molecules that regulate its architecture remain poorly understood. We identify the chromatin modifier, WDR5, as a regulator of apical F-actin in MCCs...
September 10, 2018: Developmental Cell
Shuting Wu, Rongtao Xue, Shaoli Hassan, Thi My Linh Nguyen, Tienan Wang, Hongru Pan, Jin Xu, Qifa Liu, Wenqing Zhang, Zilong Wen
Microglia are the major immune cells in the central nervous system (CNS). Born in peripheral hematopoietic tissues, microglial precursors colonize the CNS during early embryogenesis and maintain themselves thereafter. However, the mechanism underlying this colonization process remains elusive. We have recently demonstrated that neuronal apoptosis contributes to microglia colonization in zebrafish. Here, we further show that prior to neuronal apoptosis, microglial precursors are attracted to the proximal brain regions by brain-derived interleukin 34 (il34) and its receptor colony-stimulating factor 1 receptor a (csf1ra)...
September 10, 2018: Developmental Cell
Andreas Linder, Veit Hornung
The role of mitochondria as a signaling platform downstream of the RNA sensors RIG-I and MDA5 is well defined. Now, a recent study in Nature by Dhir et al. (2018) identifies mitochondrial dsRNA as an immunogenic ligand, adding another intriguing aspect to the role of mitochondria in innate immunity.
September 10, 2018: Developmental Cell
Wallace F Marshall
A recent study in Nature Cell Biology (Almuedo-Castillo et al., 2018) describes a mechanism for tissue scaling in zebrafish embryos. The authors show that a fixed relative amount of the diffusible Nodal inhibitor Lefty produces an extended gradient in larger embryos, ensuring proportionally scaled germ layers, irrespective of embryo size.
September 10, 2018: Developmental Cell
David K Breslow
Down syndrome is a developmental disorder caused by chromosome 21 trisomy, whereas ciliopathies result from defective primary cilia. In this issue of Developmental Cell, Galati et al. (2018) establish a link between these diseases, finding that cilium function is compromised in Down syndrome as a result of increased Pericentrin expression.
September 10, 2018: Developmental Cell
Hiroshi Hamada
The cellular basis of left-right asymmetric organogenesis remains largely unknown, but signaling events on the left side were thought to be dominant. In this issue of Developmental Cell, however, Sivakumar et al. (2018) suggest that covalent modification of hyaluronan on the right side initiates directional looping of the developing midgut.
September 10, 2018: Developmental Cell
Aravind Sivakumar, Aparna Mahadevan, Mark E Lauer, Ricky J Narvaez, Siddesh Ramesh, Cora M Demler, Nathan R Souchet, Vincent C Hascall, Ron J Midura, Stavros Garantziotis, David B Frank, Koji Kimata, Natasza A Kurpios
For many years, biologists have focused on the role of Pitx2, expressed on the left side of developing embryos, in governing organ laterality. Here, we identify a different pathway during left-right asymmetry initiated by the right side of the embryo. Surprisingly, this conserved mechanism is orchestrated by the extracellular glycosaminoglycan, hyaluronan (HA) and is independent of Pitx2 on the left. Whereas HA is normally synthesized bilaterally as a simple polysaccharide, we show that covalent modification of HA by the enzyme Tsg6 on the right triggers distinct cell behavior necessary to drive the conserved midgut rotation and to pattern gut vasculature...
September 10, 2018: Developmental Cell
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