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Sa Geng, Ayano Miyagi, James G Umen
Volvocine algae comprise a unique comparative model for investigating the evolution of distinct male and female sexes (oogamy) from an isogamous ancestral state with mating types. The mating-type or sex-determining gene MID encodes a putative RWP-RK family transcription factor, and orthologs of MID are present throughout the volvocine algal lineage in either the MT- or male mating locus of dioecious species. It was previously found that ectopic expression of isogamous Chlamydomonas reinhardtii MID ( CrMID ) in a C...
March 16, 2018: Development
Richard Sarro, Acadia A Kocher, Deena Emera, Severin Uebbing, Emily V Dutrow, Scott D Weatherbee, Timothy Nottoli, James P Noonan
Developmental gene expression patterns are orchestrated by thousands of distant-acting transcriptional enhancers. However, identifying enhancers essential for the expression of their target genes has proven challenging. Maps of long-range regulatory interactions may provide the means to identify enhancers critical for developmental gene expression. To investigate this hypothesis, we used circular chromosome conformation capture coupled with interaction maps in the mouse limb to characterize the regulatory topology of Pitx1 , which is essential for hindlimb development...
March 16, 2018: Development
Hyeyoon Lee, Seong-Moon Cheong, Wonhee Han, Youngmu Koo, Saet-Byeol Jo, Gun-Sik Cho, Jae-Seong Yang, Sanguk Kim, Jin-Kwan Han
Dishevelled (Dvl/Dsh) is a key scaffold protein that propagates Wnt signaling essential for embryogenesis and homeostasis. However, whether antagonism of Wnt signaling necessary for vertebrate head formation can be achieved through regulation of Dsh protein stability is unclear. Here we show that membrane-associated RING-CH2 (March2), a RING-type E3 ubiquitin ligase, antagonizes Wnt signaling by regulating the turnover of Dsh protein via ubiquitin-mediated lysosomal degradation in prospective head region of Xenopus We further found that March2 acquires regional and functional specificities for head formation from the Dsh-interacting protein Dapper1 (Dpr1)...
March 16, 2018: Development
Yu-Han Su, Elham Rastegri, Shih-Han Kao, Chun-Min Lai, Kun-Yang Lin, Hung-Yu Liao, Mu-Hsiang Wang, Hwei-Jan Hsu
Diet is an important regulator of stem cell homeostasis, however, the underlying mechanisms of this regulation are not fully known. Here, we report that insulin signaling mediates dietary maintenance of Drosophila ovarian germline stem cells (GSCs) by promoting the extension of niche escort cell (EC) membranes to wrap around GSCs. This wrapping may facilitate the delivery of BMP stemness factors from ECs in the niche to GSCs. In addition to the effects on GSCs, insulin signaling-mediated regulation of EC number and protrusions controls the division and growth of GSC progeny...
March 16, 2018: Development
M Musy, K Flaherty, J Raspopovic, A Robert-Moreno, J Richtsmeier, J Sharpe
To determine the developmental stage of embryonic mice we apply a geometric morphometric approach to the changing shape of the mouse limb bud as it grows from embryonic day 10 to embryonic day 15 post conception. As the ontogenetic sequence results in the de novo emergence of shape features not present in the early stages, we have created a standard ontogenetic trajectory for limb bud development - a quantitative characterization of shape change during limb morphogenesis. This trajectory of form as a function of time also gives us the reverse function: the ability to infer developmental stage from form, with a typical uncertainty of 2 hours...
March 14, 2018: Development
Jiejing Li, Mark Perfetto, Russell Neuner, Harinath Bahudhanapati, Laura Christian, Ketan Mathavan, Lance C Bridges, Dominique Alfandari, Shuo Wei
During vertebrate gastrulation, canonical Wnt signaling induces the formation of neural plate border (NPB). Wnt is also thought to be required for the subsequent specification of neural crest (NC) lineage at the NPB, but the direct evidence is lacking. We found previously that the disintegrin metalloproteinase ADAM13 is required for Wnt activation and NC induction in Xenopus Here we report that knockdown of ADAM13 or its close paralog ADAM19 severely downregulates Wnt activity at the NPB, inhibiting NC specification without affecting earlier NPB formation...
March 14, 2018: Development
Cheryl Q E Lee, Margherita Turco, Lucy Gardner, Benjamin Simons, Myriam Hemberger, Ashley Moffett
During pregnancy the trophoblast cells of the placenta are the only fetal cells in direct contact with maternal blood and decidua. Their functions include transport of nutrients and oxygen, secretion of pregnancy hormones, remodelling the uterine arteries, and communicating with maternal cells. Despite the importance of trophoblast cells in placental development and successful pregnancy, little is known about the identity, location and differentiation of human trophoblast progenitors. We identify a proliferative trophoblast niche at the base of the cytotrophoblast cell columns in first trimester placentas that is characterised by integrin α2 (ITGA2) expression...
March 14, 2018: Development
Sabrina Z Jan, Aldo Jongejan, Cindy M Korver, Saskia K M van Daalen, Ans M M van Pelt, Sjoerd Repping, Geert Hamer
To prevent chromosomal aberrations to be transmitted to the offspring, strict meiotic checkpoints are in place to remove aberrant spermatocytes. However, in about 1% of all males these checkpoints cause complete meiotic arrest leading to azoospermia and subsequent infertility. We here unravel two clearly distinct meiotic arrest mechanisms that act during the prophase of human male meiosis. Type I arrested spermatocytes display severe asynapsis of the homologous chromosomes, disturbed XY-body formation and increased expression of the Y-chromosome encoded gene ZFY and seem to activate a DNA damage pathway leading to induction of p63, possibly causing spermatocyte apoptosis...
March 14, 2018: Development
Sigrun Schmähling, Arno Meiler, Yoonjung Lee, Arif Mohammed, Katja Finkl, Katharina Tauscher, Lars Israel, Marc Borath, Julia Philippou-Massier, Helmut Blum, Bianca Habermann, Axel Imhof, Ji-Joon Song, Jürg Müller
The Drosophila Ash1 protein is a trithorax-group (trxG) regulator that antagonizes Polycomb repression at HOX genes. Ash1 di-methylates lysine 36 in histone H3 (H3K36me2) but how this activity is controlled and at which genes it functions is not well understood. We show that Ash1 protein purified from Drosophila exists in a complex with MRG15 and Caf1 that we named AMC. In Drosophila and human AMC, MRG15 binds a conserved FxLP motif near the Ash1 SET domain and stimulates H3K36 di-methylation on nucleosomes...
March 14, 2018: Development
Ganga Anil Kumar, Kuppuswamy Subramaniam
Pairing of homologous chromosomes is essential for genetic recombination during gametogenesis. In many organisms, chromosome ends are attached to cytoplasmic dynein, and dynein-driven chromosomal movements facilitate the pairing process. Factors that promote / control the cytoskeletal tethering of chromosomes are largely unknown. Here, we show that the conserved RNA-binding protein PUF-8 facilitates the tethering and pairing processes in the C. elegans germline by promoting proteasome activity. We have isolated a hypomorphic allele of pas-1 , which encodes a proteasome core subunit, and find that the homologous chromosomes fail to pair in the puf-8; pas-1 double mutant due to failure of chromosome tethering...
March 14, 2018: Development
Yi-Ting Lai, Kevin D Deem, Ferran Borràs-Castells, Nagraj Sambrani, Heike Rudolf, Kushal Suryamohan, Ezzat El-Sherif, Marc S Halfon, Daniel J McKay, Yoshinori Tomoyasu
Evolution of cis -regulatory elements (such as enhancers) plays an important role in the production of diverse morphology. However, a mechanistic understanding is often limited by the absence of methods to study enhancers in species outside of established model systems. Here, we sought to establish methods to identify and test enhancer activity in the red flour beetle, Tribolium castaneum To identify possible enhancer regions, we first obtained genome-wide chromatin profiles from various tissues and stages of Tribolium via FAIRE (Formaldehyde Assisted Isolation of Regulatory Elements)-sequencing...
March 14, 2018: Development
Hong Duan, Luis F de Navas, Fuqu Hu, Kailiang Sun, Yannis E Mavromatakis, Kayla Viets, Cyrus Zhou, Joshua Kavaler, Robert J Johnston, Andrew Tomlinson, Eric C Lai
Photoreceptors in the crystalline Drosophila eye are recruited by receptor tyrosine kinase (RTK)/Ras signaling, mediated by the Epidermal Growth Factor receptor (EGFR) and Sevenless receptor. Analyses of an allelic deletion series of the mir-279/996 locus, along with a panel of modified genomic rescue transgenes, show that normal Drosophila eye patterning depends on both miRNAs. Transcriptional reporter and activity sensor transgenes reveal expression and function of miR-279/996 in non-neural cells of the developing eye...
March 14, 2018: Development
Jennifer M SanMiguel, Lara K Abramowitz, Marisa S Bartolomei
Imprinted genes are expressed from one parental allele and regulated by differential DNA methylation at imprinting control regions (ICR). ICRs are reprogrammed in the germline through erasure and reestablishment of DNA methylation. Although much is known about DNA methylation establishment, DNA demethylation is less well understood. Recently, the Ten-Eleven Translocation proteins (TET1-3) have been shown to initiate DNA demethylation, with Tet1 -/- mice exhibiting aberrant levels of imprinted gene expression and ICR methylation...
March 12, 2018: Development
Jinjin Zhu, Alison Ordway, Lena Weber, Kasun Buddika, Justin P Kumar
How different cells and tissues commit and determine their fates has been a central question in developmental biology since the seminal embryological experiments conducted by Wilhelm Roux and Hans Driesch in sea urchins and frogs. Here, we demonstrate that Polycomb group (PcG) proteins maintain Drosophila eye specification by suppressing the activation of alternative fate choices. The loss of PcG in the developing eye results in a cellular reprogramming event in which the eye is redirected to a wing fate. This fate transformation occurs with either the individual loss of Pc or the simultaneous reduction of PhoRC and Pax6...
March 12, 2018: Development
Bo Zhang, Uyen Tran, Oliver Wessely
The development of the kidney relies on the establishment and maintenance of a precise tubular diameter of its functional units, the nephrons. This process is disrupted in Polycystic Kidney Disease (PKD) resulting in dilations of the nephron and renal cyst formation. In the course of exploring G-protein coupled signaling in the Xenopus pronephric kidney we discovered that loss of the G-protein alpha subunit Gnas results in a PKD phenotype. Polycystin-1, one of the genes mutated in human PKD, encodes for a protein resembling a G-protein coupled receptor...
March 12, 2018: Development
Behzad Yaghmaeian Salmani, Ignacio Monedero Cobeta, Jonathan Rakar, Susanne Bauer, Jesús Rodriguez Curt, Annika Starkenberg, Stefan Thor
A conserved feature of the central nervous system (CNS) is the prominent expansion of anterior regions (brain) when compared to posterior (nerve cord). The cellular and regulatory processes driving anterior CNS expansion are not well understood in any bilaterian species. Here, we address this expansion in Drosophila and mouse. We find that when compared to the nerve cord the brain, in both Drosophila and mouse, displays extended progenitor proliferation, more elaborate daughter cell proliferation and more rapid cell cycle speed...
March 12, 2018: Development
Mickael Orgeur, Marvin Martens, Georgeta Leonte, Sonya Nassari, Marie-Ange Bonnin, Stefan T Börno, Bernd Timmermann, Jochen Hecht, Delphine Duprez, Sigmar Stricker
Connective tissues support organs and play crucial roles in development, homeostasis and fibrosis, yet our understanding of their formation is still limited. To gain insight into the molecular mechanisms of connective tissue specification, we selected five zinc finger transcription factors - OSR1, OSR2, EGR1, KLF2 and KLF4 - based on their expression patterns and/or known involvement in connective tissue subtype differentiation. RNA-seq and ChIP-seq profiling revealed a set of common genes regulated by all five transcription factors, which we propose as connective tissue core expression set...
March 6, 2018: Development
Hiroki Goto, Miki Nishio, Yoko To, Tatsuya Oishi, Yosuke Miyachi, Tomohiko Maehama, Hiroshi Nishina, Haruhiko Akiyama, Tak Wah Mak, Yuma Makii, Taku Saito, Akihiro Yasoda, Noriyuki Tsumaki, Akira Suzuki
Hippo signaling is modulated in response to cell density, external mechanical forces, or rigidity of the extracellular matrix (ECM). The Mps one binder kinase activator (MOB) adaptor proteins are core components of Hippo signaling and have important effects on Yes-associated protein-1 (YAP1) and transcriptional co-activator with PDZ-binding motif (TAZ), which are potent transcriptional regulators. YAP1/TAZ are key contributors to cartilage and bone development but the molecular mechanisms by which the Hippo pathway controls chondrogenesis are largely unknown...
March 6, 2018: Development
Rémi-Xavier Coux, Felipe Karam Teixeira, Ruth Lehmann
Maintenance of cellular identity is essential for tissue development and homeostasis. At the molecular level, cell identity is determined by the coordinated activation and repression of defined sets of genes. The tumor suppressor L(3)mbt was shown to secure cellular identity in Drosophila larval brains by repressing germline-specific genes. Here we interrogate the temporal and spatial requirements for L(3)mbt in the Drosophila ovary, and show that it safeguards the integrity of both somatic and germline tissues...
March 6, 2018: Development
C M McQueen, E E Schmitt, T R Sarkar, J Elswood, R P Metz, D Earnest, M Rijnkels, W W Porter
The molecular clock plays key roles in daily physiological functions, development, and cancer. Period 2 (PER2) is a repressive element, which inhibits transcription activated by positive clock elements, resulting in diurnal cycling of genes. However, there are gaps in our understanding of the role of the clock in normal development outside of its time keeping function. Here we show that PER2 has a non-circadian function that is critical to mammary gland development. Virgin Per2 deficient mice, Per2 -/- , have underdeveloped glands containing fewer bifurcations and terminal ducts...
February 28, 2018: Development
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