Growth/Differentiation Factor 3 Signals Through ALK7 and Regulates Accumulation of Adipose Tissue and Diet-Induced Obesity
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Supplemental Table 1. Complete Gene Lists and GO Terms from Figure 3C
Supplemental Table 1. Complete gene lists and GO terms from Figure 3C. Path 1 Genes: RP11-34P13.15, RP4-758J18.10, VWA1, CHD5, AZIN2, FOXO6, RP11-403I13.8, ARHGAP30, RGS4, LRRN2, RASSF5, SERTAD4, GJC2, RHOU, REEP1, FOXI3, SH3RF3, COL4A4, ZDHHC23, FGFR3, PPP2R2C, CTD-2031P19.4, RNF182, GRM4, PRR15, DGKI, CHMP4C, CALB1, SPAG1, KLF4, ENG, RET, GDF10, ADAMTS14, SPOCK2, MBL1P, ADAM8, LRP4-AS1, CARNS1, DGAT2, CRYAB, AP000783.1, OPCML, PLEKHG6, GDF3, EMP1, RASSF9, FAM101A, STON2, GREM1, ACTC1, CORO2B, FURIN, WFIKKN1, BAIAP3, TMC5, HS3ST4, ZFHX3, NLRP1, RASD1, CACNG4, EMILIN2, L3MBTL4, KLHL14, HMSD, RP11-849I19.1, SALL3, GADD45B, KANK3, CTC- 526N19.1, ZNF888, MMP9, BMP7, PIK3IP1, MCHR1, SYTL5, CAMK2N1, PINK1, ID3, PTPRU, MANEAL, MCOLN3, LRRC8C, NTNG1, KCNC4, RP11, 430C7.5, C1orf95, ID2-AS1, ID2, GDF7, KCNG3, RGPD8, PSD4, CCDC74B, BMPR2, KAT2B, LINC00693, ZNF654, FILIP1L, SH3TC1, CPEB2, NPFFR2, TRPC3, RP11-752L20.3, FAM198B, TLL1, CDH9, PDZD2, CHSY3, GALNT10, FOXQ1, ATXN1, ID4, COL11A2, CNR1, GTF2IP4, FZD1, PAX5, RP11-35N6.1, UNC5B, NKX1-2, FAM196A, EBF3, PRRG4, LRP4, SYT7, PLBD1, GRASP, ALX1, HIP1R, LPAR6, SLITRK6, C16orf89, RP11-491F9.1, MMP2, B3GNT9, NXPH3, TNRC6C-AS1, LDLRAD4, NOL4, SMAD7, HCN2, PDE4A, KANK2, SAMD1, EXOC3L2, IL11, EMILIN3, KCNB1, DOK5, EEF1A2, A4GALT, ADGRG2, ELF4, ABCD1 Term Count % PValue Genes regulation of pathway-restricted GDF3, SMAD7, GDF7, BMPR2, GDF10, GREM1, BMP7, LDLRAD4, SMAD protein phosphorylation 9 6.34 1.31E-08 ENG pathway-restricted SMAD protein GDF3, SMAD7, GDF7, BMPR2, GDF10, GREM1, BMP7, LDLRAD4, phosphorylation -
Nodal Signaling Is Required for Mesodermal and Ventral but Not For
© 2015. Published by The Company of Biologists Ltd | Biology Open (2015) 4, 830-842 doi:10.1242/bio.011809 RESEARCH ARTICLE Nodal signaling is required for mesodermal and ventral but not for dorsal fates in the indirect developing hemichordate, Ptychodera flava Eric Röttinger1,2,3,*, Timothy Q. DuBuc4, Aldine R. Amiel1,2,3 and Mark Q. Martindale4 ABSTRACT early fate maps of direct and indirect developing hemichordates, are Nodal signaling plays crucial roles in vertebrate developmental similar to those of indirect-developing echinoids (Colwin and processes such as endoderm and mesoderm formation, and axial Colwin, 1951; Cameron et al., 1987; Cameron et al., 1989; Cameron patterning events along the anteroposterior, dorsoventral and left- and Davidson, 1991; Henry et al., 2001). While the bilaterally right axes. In echinoderms, Nodal plays an essential role in the symmetric echinoderm larvae exhibit strong similarities to establishment of the dorsoventral axis and left-right asymmetry, but chordates in axial patterning and germ layer specification events, not in endoderm or mesoderm induction. In protostomes, Nodal adult body plan comparisons in echinoderms have been difficult due signaling appears to be involved only in establishing left-right to their unique adult pentaradial symmetry. However, both the larval asymmetry. Hence, it is hypothesized that Nodal signaling has and adult body plans of enteropneust hemichordates are bilaterally been co-opted to pattern the dorsoventral axis of deuterostomes and symmetric, and larvae from indirect developing hemichordates for endoderm, mesoderm formation as well as anteroposterior such as Ptychodera flava (P. flava) share similarities in patterning in chordates. Hemichordata, together with echinoderms, morphology, axial organization, and developmental fate map with represent the sister taxon to chordates. -
TGF Beta Signaling Pathways and Microrna Function in the Female Reproductive Tract
TGF Beta signaling pathways and microRNA function in the female reproductive tract Prof. Martin Matzuk Baylor College of Medicine Intellectual and Developmental Disabilities Research Center Houston, TX, USA TGFb signaling pathways and microRNA function in the female reproductive tract Topic 1 TGFb Superfamily N Pro RRRR Mature C • Largest family of growth factor ligands in mammals • Function as secreted homodimers or heterodimers in multiple developmental and physiologic processes • We have been studying 12 family members including growth differentiation factor 9 (GDF9), bone morphogenetic protein 15 (BMP15), activins, inhibins, and GDF3 GDF9 functions in folliculogenesis & cumulus expansion Pre-Ovulatory Follicle Cumulus GC Early Antral Follicle Ovulating Follicle Mural GC Fertilization Secondary & Embryo Follicle Development GDF9 KO Primary Primordial Follicle Follicles Dong et. al. Nature 1996 Elvin et al. Mol Endo, 1999a, b TGFb Superfamily “Canonical” Signaling Pathways – GDF9 and BMP15 appear to signal in different pathways GDF9/BMP b b Extracellular Cytoplasm Type II Type I (Kinase) (Kinase) “BMP” SMAD1/5/8 SMAD2/3 “Activin/TGFb” Pathway SMAD4 SMAD4 Pathway (BMP15) (GDF9) Nucleus BMP-Specific Activin-Specific Genes Genes What is the ovarian GDF9 type 1 receptor? ALK1 Activin receptor like-1 ALK2 Activin receptor 1 ALK3 BMP receptor 1A ALK4 Activin receptor 1B ALK5 TGFb receptor 1 ALK6 BMP receptor 1B ALK7 Activin receptor 1C b b Extracellular Cytoplasm Type II Type I (Kinase) (Kinase) “BMP” ALK2, ALK5, “GDF9” Pathway ALK3, ALK6 -
The Transcriptional Co-Regulator Jab1 Is Crucial for Chondrocyte
234 Research Article The transcriptional co-regulator Jab1 is crucial for chondrocyte differentiation in vivo Dongxing Chen1, Lindsay A. Bashur1, Bojian Liang1,*, Martina Panattoni2, Keiko Tamai3,`, Ruggero Pardi2 and Guang Zhou1,3,4,§ 1Department of Orthopaedics, Case Western Reserve University, 10900 Euclid Avenue, Cleveland, OH 44106, USA 2San Raffaele University, School of Medicine and Scientific Institute San Raffaele, Milan, Italy 3Department of Genetics, Case Western Reserve University, 10900 Euclid Avenue, Cleveland, OH 44106, USA 4Case Comprehensive Cancer Center, Case Western Reserve University, 10900 Euclid Avenue, Cleveland, OH 44106, USA *Present address: Department of Orthopaedics, China-Japan Union Hospital, Jilin University, Changchun, Jilin Province, People’s Republic of China `Present address: Oncology Research Laboratories, Daiichi Sankyo Co., Ltd.., Tokyo, Japan §Author for correspondence ([email protected]) Accepted 11 November 2012 Journal of Cell Science 126, 234–243 ß 2013. Published by The Company of Biologists Ltd doi: 10.1242/jcs.113795 Summary The evolutionarily conserved transcriptional cofactor Jab1 plays critical roles in cell differentiation, proliferation, and apoptosis by modulating the activity of diverse factors and regulating the output of various signaling pathways. Although Jab1 can interact with the bone morphogenetic protein (BMP) downstream effector Smad5 to repress BMP signaling in vitro, the role of Jab1 in BMP-mediated skeletogenesis in vivo is still poorly understood. As a key regulator of skeletogenesis, BMP signaling regulates the critical Ihh-Pthrp feedback loop to promote chondrocyte hypertrophy. In this study, we utilized the loxP/Cre system to delineate the specific role of Jab1 in cartilage formation. Strikingly, Jab1 chondrocyte-specific knockout Jab1flox/flox; Col2a1-Cre (cKO) mutants exhibited neonatal lethal chondrodysplasia with severe dwarfism. -
Cerberus–Nodal–Lefty–Pitx Signaling Cascade Controls Left–Right Asymmetry in Amphioxus
Cerberus–Nodal–Lefty–Pitx signaling cascade controls left–right asymmetry in amphioxus Guang Lia,1, Xian Liua,1, Chaofan Xinga, Huayang Zhanga, Sebastian M. Shimeldb,2, and Yiquan Wanga,2 aState Key Laboratory of Cellular Stress Biology, School of Life Sciences, Xiamen University, Xiamen, Fujian 361102, China; and bDepartment of Zoology, University of Oxford, Oxford OX1 3PS, United Kingdom Edited by Marianne Bronner, California Institute of Technology, Pasadena, CA, and approved February 21, 2017 (received for review December 14, 2016) Many bilaterally symmetrical animals develop genetically pro- Several studies have sought to dissect the evolutionary history of grammed left–right asymmetries. In vertebrates, this process is un- Nodal signaling and its regulation of LR asymmetry. Notably, der the control of Nodal signaling, which is restricted to the left side asymmetric expression of Nodal and Pitx in gastropod mollusc by Nodal antagonists Cerberus and Lefty. Amphioxus, the earliest embryos plays a role in the development of LR asymmetry, in- diverging chordate lineage, has profound left–right asymmetry as cluding the coiling of the shell (5, 6). Asymmetric expression of alarva.WeshowthatCerberus, Nodal, Lefty, and their target Nodal and/or Pitx has also been reported in some other lopho- transcription factor Pitx are sequentially activated in amphioxus trochozoans, including Pitx in a brachiopod and an annelid and embryos. We then address their function by transcription activa- Nodal in a brachiopod (7, 8). These data can be interpreted to tor-like effector nucleases (TALEN)-based knockout and heat-shock suggest an ancestral role for Nodal and Pitx in regulating bilat- promoter (HSP)-driven overexpression. -
The Genetic Factors of Bilaterian Evolution Peter Heger1*, Wen Zheng1†, Anna Rottmann1, Kristen a Panfilio2,3, Thomas Wiehe1
RESEARCH ARTICLE The genetic factors of bilaterian evolution Peter Heger1*, Wen Zheng1†, Anna Rottmann1, Kristen A Panfilio2,3, Thomas Wiehe1 1Institute for Genetics, Cologne Biocenter, University of Cologne, Cologne, Germany; 2Institute for Zoology: Developmental Biology, Cologne Biocenter, University of Cologne, Cologne, Germany; 3School of Life Sciences, University of Warwick, Gibbet Hill Campus, Coventry, United Kingdom Abstract The Cambrian explosion was a unique animal radiation ~540 million years ago that produced the full range of body plans across bilaterians. The genetic mechanisms underlying these events are unknown, leaving a fundamental question in evolutionary biology unanswered. Using large-scale comparative genomics and advanced orthology evaluation techniques, we identified 157 bilaterian-specific genes. They include the entire Nodal pathway, a key regulator of mesoderm development and left-right axis specification; components for nervous system development, including a suite of G-protein-coupled receptors that control physiology and behaviour, the Robo- Slit midline repulsion system, and the neurotrophin signalling system; a high number of zinc finger transcription factors; and novel factors that previously escaped attention. Contradicting the current view, our study reveals that genes with bilaterian origin are robustly associated with key features in extant bilaterians, suggesting a causal relationship. *For correspondence: [email protected] Introduction The taxon Bilateria consists of multicellular animals -
ISM1 Regulates NODAL Signaling and Asymmetric Organ Morphogenesis During Development
Published Online: 6 June, 2019 | Supp Info: http://doi.org/10.1083/jcb.201801081 Downloaded from jcb.rupress.org on June 6, 2019 ARTICLE ISM1 regulates NODAL signaling and asymmetric organ morphogenesis during development Liliana Osório1,2*,XueweiWu1,2*, Linsheng Wang1,2*, Zhixin Jiang1,2,CarlosNeideck1,2, Guojun Sheng3,4, and Zhongjun Zhou1,2 Isthmin1 (ISM1) was originally identified as a fibroblast group factor expressed in Xenopus laevis embryonic brain, but its biological functions remain unclear. The spatiotemporal distribution of ISM1, with high expression in the anterior primitive streak of the chick embryo and the anterior mesendoderm of the mouse embryo, suggested that ISM1 may regulate signaling by the NODAL subfamily of TGB-β cytokines that control embryo patterning. We report that ISM1 is an inhibitor of NODAL signaling. ISM1 has little effect on TGF-β1, ACTIVIN-A, or BMP4 signaling but specifically inhibits NODAL-induced phosphorylation of SMAD2. In line with this observation, ectopic ISM1 causes defective left-right asymmetry and abnormal heart positioning in chick embryos. Mechanistically, ISM1 interacts with NODAL ligand and type I receptor ACVR1B through its AMOP domain, which compromises the NODAL–ACVR1B interaction and down-regulates phosphorylation of SMAD2. Therefore, we identify ISM1 as an extracellular antagonist of NODAL and reveal a negative regulatory mechanism that provides greater plasticity for the fine-tuning of NODAL signaling. Introduction The TGF-β superfamily includes a large number of secreted whereas GDF3 is an essential coligand for NODAL signaling in signaling factors that are essential for embryonic development, germ layer formation and LR patterning during early develop- tissue homeostasis, and human diseases such as cancer ment (Levine et al., 2009; Peterson et al., 2013; Pelliccia et al., (Wakefield and Hill, 2013). -
TGF-Β Signaling
biomolecules Review TGF-β Signaling Kalliopi Tzavlaki and Aristidis Moustakas * Department of Medical Biochemistry and Microbiology, Science for Life Laboratory, Uppsala University, Box 582, SE-751 23 Uppsala, Sweden; [email protected] * Correspondence: [email protected]; Tel.: +46-18-4714732; Fax: +46-18-4714441 Received: 18 February 2020; Accepted: 20 March 2020; Published: 23 March 2020 Abstract: Transforming growth factor-β (TGF-β) represents an evolutionarily conserved family of secreted polypeptide factors that regulate many aspects of physiological embryogenesis and adult tissue homeostasis. The TGF-β family members are also involved in pathophysiological mechanisms that underlie many diseases. Although the family comprises many factors, which exhibit cell type-specific and developmental stage-dependent biological actions, they all signal via conserved signaling pathways. The signaling mechanisms of the TGF-β family are controlled at the extracellular level, where ligand secretion, deposition to the extracellular matrix and activation prior to signaling play important roles. At the plasma membrane level, TGF-βs associate with receptor kinases that mediate phosphorylation-dependent signaling to downstream mediators, mainly the SMAD proteins, and mediate oligomerization-dependent signaling to ubiquitin ligases and intracellular protein kinases. The interplay between SMADs and other signaling proteins mediate regulatory signals that control expression of target genes, RNA processing at multiple levels, mRNA translation and nuclear or cytoplasmic protein regulation. This article emphasizes signaling mechanisms and the importance of biochemical control in executing biological functions by the prototype member of the family, TGF-β. Keywords: extracellular matrix; phosphorylation; receptor serine/threonine kinase; signal transduction; SMAD; transcription; transforming growth factor-β; ubiquitylation 1. -
The Nuclear Receptor REVERB Represses the Transcription of Growthdifferentiation Factor 10 and 15 Genes in Rat Endometrium Strom
Physiological Reports ISSN 2051-817X ORIGINAL RESEARCH The nuclear receptor REV-ERBa represses the transcription of growth/differentiation factor 10 and 15 genes in rat endometrium stromal cells Lijia Zhao1, Keishiro Isayama1, Huatao Chen1,*, Nobuhiko Yamauchi1, Yasufumi Shigeyoshi2, Seiichi Hashimoto3 & Masa-aki Hattori1 1 Department of Animal and Marine Bioresource Sciences, Graduate School of Agriculture, Kyushu University, Fukuoka, Japan 2 Department of Anatomy and Neurobiology, Kinki University School of Medicine, Osaka, Japan 3 Graduate School of Medicine, The University of Tokyo, Tokyo, Japan Keywords Abstract Circadian clock, decidualization, growth/ differentiation factors, REV-ERBa. Cellular oscillators in the uterus play critical roles in the gestation processes of mammals through entraining of the clock proteins to numerous downstream Correspondence genes, including growth/differentiation factor (Gdf)10 and Gdf15. The expres- Masa-aki Hattori, Department of Animal and sion of Gdf10 and Gdf15 is significantly increased in the uterus during decidu- Marine Bioresource Sciences, Graduate alization, but the mechanism underlying the regulation of Gdf gene expression School of Agriculture, Kyushu University, in the uterus is poorly understood. Here, we focused on the function of the Hakozaki, Higashi-ku, Fukuoka 812-8581, cellular oscillators in the expression of Gdf family by using uterine endome- Japan. Tel: +81-92-642-2938 trial stromal cells (UESCs) isolated from pregnant Per2-dLuc transgenic rats. Fax: +81-92-642-2938 A significant decline of Per2-dLuc bioluminescence activity was induced in E-mail: [email protected] in vitro decidualized UESCs, and concomitantly the expression of canonical clock genes was downregulated. Conversely, the expression of Gdf10 and ⁄ Present address Gdf15 of the Gdf was upregulated. -
Vg1-Nodal Heterodimers Are the Endogenous Inducers of Mesendoderm Tessa G Montague1*, Alexander F Schier1,2,3,4,5*
RESEARCH ARTICLE Vg1-Nodal heterodimers are the endogenous inducers of mesendoderm Tessa G Montague1*, Alexander F Schier1,2,3,4,5* 1Department of Molecular and Cellular Biology, Harvard University, Cambridge, United States; 2Center for Brain Science, Harvard University, Cambridge, United States; 3Broad Institute of MIT and Harvard, Cambridge, United States; 4Harvard Stem Cell Institute, Cambridge, United States; 5FAS Center for Systems Biology, Harvard University, Cambridge, United States Abstract Nodal is considered the key inducer of mesendoderm in vertebrate embryos and embryonic stem cells. Other TGF-beta-related signals, such as Vg1/Dvr1/Gdf3, have also been implicated in this process but their roles have been unclear or controversial. Here we report that zebrafish embryos without maternally provided vg1 fail to form endoderm and head and trunk mesoderm, and closely resemble nodal loss-of-function mutants. Although Nodal is processed and secreted without Vg1, it requires Vg1 for its endogenous activity. Conversely, Vg1 is unprocessed and resides in the endoplasmic reticulum without Nodal, and is only secreted, processed and active in the presence of Nodal. Co-expression of Nodal and Vg1 results in heterodimer formation and mesendoderm induction. Thus, mesendoderm induction relies on the combination of two TGF-beta- related signals: maternal and ubiquitous Vg1, and zygotic and localized Nodal. Modeling reveals that the pool of maternal Vg1 enables rapid signaling at low concentrations of zygotic Nodal. DOI: https://doi.org/10.7554/eLife.28183.001 Introduction *For correspondence: tessa. [email protected] (TGM); The induction of mesoderm and endoderm (mesendoderm) during embryogenesis and embryonic [email protected] (AFS) stem cell differentiation generates the precursors of the heart, liver, gut, pancreas, kidney and other internal organs. -
The New Role of TGF-Β Superfamily Signaling in Melanoma
Zurich Open Repository and Archive University of Zurich Main Library Strickhofstrasse 39 CH-8057 Zurich www.zora.uzh.ch Year: 2017 The new role of TGF- superfamily signaling in melanoma Tuncer, Eylül Posted at the Zurich Open Repository and Archive, University of Zurich ZORA URL: https://doi.org/10.5167/uzh-148195 Dissertation Published Version Originally published at: Tuncer, Eylül. The new role of TGF- superfamily signaling in melanoma. 2017, University of Zurich, Faculty of Science. The New Role of TGF-β Superfamily Signaling in Melanoma Dissertation zur Erlangung der naturwissenschaftlichen Doktorwürde (Dr. sc. nat.) vorgelegt der Mathematisch-naturwissenschaftlichen Fakultät der Universität Zürich von Eylül Tuncer Aus der Türkei Promotionskommission Prof. Dr. Lukas Sommer (Leitung und Vorsitz der Dissertation) Prof. Dr. med. Onur Boyman Prof. Dr. med. Markus Manz Prof. Dr. Burkhard Becher Zürich, 2017 Table of Contents Table of Contents ......................................................................................................... 2 1. Summary .................................................................................................................. 5 2. Zusammenfassung ..................................................................................................... 6 3. Introduction .............................................................................................................. 8 3.1 Definition and Epidemiology of Cutaneous Melanoma ................................................ 8 3.2 Clinical -
The Regulation of Mesodermal Progenitor Cell Commitment to Somitogenesis Subdivides the Zebrafish Body Musculature Into Distinct Domains
Downloaded from genesdev.cshlp.org on September 24, 2021 - Published by Cold Spring Harbor Laboratory Press The regulation of mesodermal progenitor cell commitment to somitogenesis subdivides the zebrafish body musculature into distinct domains Daniel P. Szeto1 and David Kimelman2 Department of Biochemistry, University of Washington, Seattle, Washington 98195, USA The vertebrate musculature is produced from a visually uniform population of mesodermal progenitor cells (MPCs) that progressively bud off somites populating the trunk and tail. How the MPCs are regulated to continuously release cells into the presomitic mesoderm throughout somitogenesis is not understood. Using a genetic approach to study the MPCs, we show that a subset of MPCs are set aside very early in zebrafish development, and programmed to cell-autonomously enter the tail domain beginning with the 16th somite. Moreover, we show that the trunk is subdivided into two domains, and that entry into the anterior trunk, posterior trunk, and tail is regulated by interactions between the Nodal and bone morphogenetic protein (Bmp) pathways. Finally, we show that the tail MPCs are held in a state we previously called the Maturation Zone as they wait for the signal to begin entering somitogenesis. [Keywords: Bmp signaling; Nodal; T-box genes; MZoep; somite] Supplemental material is available at http://www.genesdev.org. Received March 29, 2006; revised version accepted May 12, 2006. The mesodermal progenitor cells (MPCs) are a popula- the presomitic mesoderm (Griffin and Kimelman 2002) tion of undifferentiated progenitor cells that originate in (this zone is not the same as the maturation front at the the early gastrula embryo (for review, see Schier et al.