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Spemann Organizer Transcriptome Induction by Early Beta-Catenin, Wnt
Spemann organizer transcriptome induction by early PNAS PLUS beta-catenin, Wnt, Nodal, and Siamois signals in Xenopus laevis Yi Dinga,b,1, Diego Plopera,b,1, Eric A. Sosaa,b, Gabriele Colozzaa,b, Yuki Moriyamaa,b, Maria D. J. Beniteza,b, Kelvin Zhanga,b, Daria Merkurjevc,d,e, and Edward M. De Robertisa,b,2 aHoward Hughes Medical Institute, University of California, Los Angeles, CA 90095-1662; bDepartment of Biological Chemistry, University of California, Los Angeles, CA 90095-1662; cDepartment of Medicine, University of California, Los Angeles, CA 90095-1662; dDepartment of Microbiology, University of California, Los Angeles, CA 90095-1662; and eDepartment of Human Genetics, University of California, Los Angeles, CA 90095-1662 Contributed by Edward M. De Robertis, February 24, 2017 (sent for review January 17, 2017; reviewed by Juan Larraín and Stefano Piccolo) The earliest event in Xenopus development is the dorsal accumu- Wnt8 mRNA leads to a dorsalized phenotype consisting entirely of lation of nuclear β-catenin under the influence of cytoplasmic de- head structures without trunks and a radial Spemann organizer terminants displaced by fertilization. In this study, a genome-wide (9–11). Similar dorsalizing effects are obtained by incubating approach was used to examine transcription of the 43,673 genes embryos in lithium chloride (LiCl) solution at the 32-cell stage annotated in the Xenopus laevis genome under a variety of con- (12). LiCl mimics the early Wnt signal by inhibiting the enzymatic ditions that inhibit or promote formation of the Spemann orga- activity of glycogen synthase kinase 3 (GSK3) (13), an enzyme nizer signaling center. -
Access AMH Instructions for Use Anti-Müllerian Hormone (AMH) © 2017 Beckman Coulter, Inc
ACCESS Immunoassay Systems Access AMH Instructions For Use Anti-Müllerian hormone (AMH) © 2017 Beckman Coulter, Inc. All rights reserved. B13127 FOR PROFESSIONAL USE ONLY Rx Only ANNUAL REVIEW Reviewed by Date Reviewed by Date PRINCIPLE INTENDED USE The Access AMH assay is a paramagnetic particle chemiluminescent immunoassay for the quantitative determination of anti-Müllerian hormone (AMH) levels in human serum and lithium heparin plasma using the Access Immunoassay Systems as an aid in the assessment of ovarian reserve in women presenting to fertility clinics. This system is intended to distinguish between women presenting with AFC (antral follicle count) values > 15 (high ovarian reserve) and women with AFC values ≤ 15 (normal or diminished ovarian reserve). The Access AMH is intended to be used in conjunction with other clinical and laboratory findings such as antral follicle count, before starting fertility therapy. The Access AMH is not intended to be used for monitoring of women undergoing controlled ovarian stimulation in an Assisted Reproduction Technology program. SUMMARY AND EXPLANATION Anti-Müllerian hormone (AMH) is a glycoprotein, which circulates as a dimer composed of two identical 72 kDa monomers that are linked by disulfide bridges. AMH belongs to the transforming growth factor-β family.1,2 AMH is named for its first described function in fetal sexual differentiation: a regression of the Müllerian ducts in males during early fetal life. In males, AMH is secreted by Sertoli cells of the testes. AMH concentrations are high -
Follistatin and Noggin Are Excluded from the Zebrafish Organizer
DEVELOPMENTAL BIOLOGY 204, 488–507 (1998) ARTICLE NO. DB989003 Follistatin and Noggin Are Excluded from the Zebrafish Organizer Hermann Bauer,* Andrea Meier,* Marc Hild,* Scott Stachel,†,1 Aris Economides,‡ Dennis Hazelett,† Richard M. Harland,† and Matthias Hammerschmidt*,2 *Max-Planck Institut fu¨r Immunbiologie, Stu¨beweg 51, 79108 Freiburg, Germany; †Department of Molecular and Cell Biology, University of California, 401 Barker Hall 3204, Berkeley, California 94720-3204; and ‡Regeneron Pharmaceuticals, Inc., 777 Old Saw Mill River Road, Tarrytown, New York 10591-6707 The patterning activity of the Spemann organizer in early amphibian embryos has been characterized by a number of organizer-specific secreted proteins including Chordin, Noggin, and Follistatin, which all share the same inductive properties. They can neuralize ectoderm and dorsalize ventral mesoderm by blocking the ventralizing signals Bmp2 and Bmp4. In the zebrafish, null mutations in the chordin gene, named chordino, lead to a severe reduction of organizer activity, indicating that Chordino is an essential, but not the only, inductive signal generated by the zebrafish organizer. A second gene required for zebrafish organizer function is mercedes, but the molecular nature of its product is not known as yet. To investigate whether and how Follistatin and Noggin are involved in dorsoventral (D-V) patterning of the zebrafish embryo, we have now isolated and characterized their zebrafish homologues. Overexpression studies demonstrate that both proteins have the same dorsalizing properties as their Xenopus homologues. However, unlike the Xenopus genes, zebrafish follistatin and noggin are not expressed in the organizer region, nor are they linked to the mercedes mutation. Expression of both genes starts at midgastrula stages. -
Differential Compartmentalization of BMP4/NOGGIN Requires NOGGIN Trans-Epithelial Transport
bioRxiv preprint doi: https://doi.org/10.1101/2020.12.18.423440; this version posted December 19, 2020. The copyright holder for this preprint (which was not certified by peer review) is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under aCC-BY-ND 4.0 International license. Differential compartmentalization of BMP4/NOGGIN requires NOGGIN trans-epithelial transport Tien Phan-Everson1-2 +, Fred Etoc1 +, Ali H. Brivanlou1 *, Eric D. Siggia2 * 1 Laboratory of Stem Cell Biology and Molecular Embryology, The Rockefeller University, New York, New York 10065, USA. 2 Laboratory of Physical, Mathematical, and Computational Biology, The Rockefeller University, New York, New York 10065, USA. + Co-first Authors * Joint Corresponding Authors Correspondence: [email protected]; [email protected] Summary Using self-organizing human models of gastrulation, we previously showed that (i) BMP4 initiates the cascade of events leading to gastrulation; (ii) BMP4 signal-reception is restricted to the basolateral domain; and (iii) in a human-specific manner, BMP4 directly induces the expression of NOGGIN. Here, we report the surprising discovery that in human epiblasts, NOGGIN and BMP4 were secreted into opposite extracellular spaces. Interestingly, apically-presented NOGGIN could inhibit basally-delivered BMP4. Apically-imposed microfluidic flow demonstrated that NOGGIN traveled in the apical extracellular space. Our co-localization analysis detailed the endocytotic route that trafficked NOGGIN from the apical space to the basolateral intercellular space where BMP4 receptors were located. This apical-to-basal transcytosis was indispensable for NOGGIN inhibition. Taken together, the segregation of activator/inhibitor into distinct extracellular spaces challenges classical views of morphogen movement. -
Novel Roles of Follistatin/Myostatin in Transforming Growth Factor-Β
UCLA UCLA Previously Published Works Title Novel Roles of Follistatin/Myostatin in Transforming Growth Factor-β Signaling and Adipose Browning: Potential for Therapeutic Intervention in Obesity Related Metabolic Disorders. Permalink https://escholarship.org/uc/item/2sv437dw Authors Pervin, Shehla Reddy, Srinivasa T Singh, Rajan Publication Date 2021 DOI 10.3389/fendo.2021.653179 Peer reviewed eScholarship.org Powered by the California Digital Library University of California REVIEW published: 09 April 2021 doi: 10.3389/fendo.2021.653179 Novel Roles of Follistatin/Myostatin in Transforming Growth Factor-b Signaling and Adipose Browning: Potential for Therapeutic Intervention in Obesity Related Metabolic Disorders Shehla Pervin 1,2, Srinivasa T. Reddy 3,4 and Rajan Singh 1,2,5* 1 Department of Obstetrics and Gynecology, David Geffen School of Medicine at University of California Los Angeles (UCLA), Los Angeles, CA, United States, 2 Division of Endocrinology and Metabolism, Charles R. Drew University of Medicine and Edited by: Science, Los Angeles, CA, United States, 3 Department of Molecular and Medical Pharmacology, David Geffen School of Xinran Ma, Medicine at UCLA, Los Angeles, CA, United States, 4 Department of Medicine, Division of Cardiology, David Geffen School of East China Normal University, China Medicine, University of California Los Angeles, Los Angeles, CA, United States, 5 Department of Endocrinology, Men’s ’ Reviewed by: Health: Aging and Metabolism, Brigham and Women s Hospital, Boston, MA, United States Meng Dong, Institute of Zoology, Chinese Obesity is a global health problem and a major risk factor for several metabolic conditions Academy of Sciences (CAS), China Abir Mukherjee, including dyslipidemia, diabetes, insulin resistance and cardiovascular diseases. -
Lack of Tgfbr1 and Acvr1b Synergistically Stimulates Myofibre Hypertrophy And
bioRxiv preprint doi: https://doi.org/10.1101/2021.03.03.433740; this version posted March 6, 2021. The copyright holder for this preprint (which was not certified by peer review) is the author/funder. All rights reserved. No reuse allowed without permission. Lack of Tgfbr1 and Acvr1b synergistically stimulates myofibre hypertrophy and accelerates muscle regeneration *M.M.G. Hillege1, *A. Shi1,2 ,3, R.C. Galli Caro1, G. Wu4, P. Bertolino5, W.M.H. Hoogaars1,6, R.T. Jaspers1 1. Laboratory for Myology, Department of Human Movement Sciences, Faculty of Behavioural and Movement Sciences, Vrije Universiteit Amsterdam, Amsterdam Movement Sciences, Amsterdam, The Netherlands 2. Department of Oral and Maxillofacial Surgery/Pathology, Amsterdam UMC and Academic Center for Dentistry Amsterdam (ACTA), Vrije Universiteit Amsterdam (VU), Amsterdam Movement Sciences (AMS), Amsterdam, the Netherlands 3. Key Laboratory of Oral Medicine, Guangzhou Institute of Oral Disease, Affiliated Stomatology Hospital of Guangzhou Medical University, Guangzhou Medical University, Guangzhou, China 4. Department of Oral Implantology and Prosthetic Dentistry, Academic Centre for Dentistry Amsterdam (ACTA), University of Amsterdam (UvA) and Vrije Universiteit Amsterdam (VU), The Netherlands 5. Centre de Recherche en Cancérologie de Lyon, UMR INSERM U1052/CNRS 5286, Université de Lyon, Centre Léon Bérard, Lyon, France 6. European Research Institute for the Biology of Ageing (ERIBA), University Medical Center Groningen (UMCG), University of Groningen, Groningen, The Netherlands *Contributed equally to this manuscript **Correspondence: [email protected]; Tel.: +31 (0) 205988463 1 bioRxiv preprint doi: https://doi.org/10.1101/2021.03.03.433740; this version posted March 6, 2021. The copyright holder for this preprint (which was not certified by peer review) is the author/funder. -
Effective Inhibition of Bone Morphogenetic Protein Function By
Published OnlineFirst September 8, 2015; DOI: 10.1158/1535-7163.MCT-14-0956 Small Molecule Therapeutics Molecular Cancer Therapeutics Effective Inhibition of Bone Morphogenetic Protein Function by Highly Specific Llama-Derived Antibodies Silvia Calpe1, Koen Wagner2, Mohamed El Khattabi3, Lucy Rutten3, Cheryl Zimberlin4, Edward Dolk3, C. Theo Verrips3, Jan Paul Medema4, Hergen Spits2, and Kausilia K. Krishnadath1,5 Abstract Bone morphogenetic proteins (BMP) have important but signaling. Epitope binning and docking modeling have shed distinct roles in tissue homeostasis and disease, including light into the basis for their BMP specificity. As opposed to the carcinogenesis and tumor progression. A large number of BMP wide structural reach of natural inhibitors, these small mole- inhibitors are available to study BMP function; however, as culestargetthegroovesandpocketsofBMPsinvolvedin most of these antagonists are promiscuous, evaluating specific receptor binding. In organoid experiments, specific inhibition effectsofindividualBMPsisnotfeasible.Becausetheonco- of BMP4 does not affect the activation of normal stem cells. genic role of the different BMPs varies for each neoplasm, Furthermore, in vitro inhibition of cancer-derived BMP4 non- highly selective BMP inhibitors are required. Here, we describe canonical signals results in an increase of chemosensitivity the generation of three types of llama-derived heavy chain in a colorectal cancer cell line. Therefore, because of their variable domains (VHH) that selectively bind to either BMP4, high specificity and low off-target effects, these VHHs could þ to BMP2 and 4, or to BMP2, 4, 5, and 6. These generated VHHs represent a therapeutic alternative for BMP4 malignancies. have high affinity to their targets and are able to inhibit BMP Mol Cancer Ther; 14(11); 2527–40. -
The Pitx2:Mir-200C/141:Noggin Pathway Regulates Bmp Signaling
3348 RESEARCH ARTICLE STEM CELLS AND REGENERATION Development 140, 3348-3359 (2013) doi:10.1242/dev.089193 © 2013. Published by The Company of Biologists Ltd The Pitx2:miR-200c/141:noggin pathway regulates Bmp signaling and ameloblast differentiation Huojun Cao1,*, Andrew Jheon2,*, Xiao Li1, Zhao Sun1, Jianbo Wang1, Sergio Florez1, Zichao Zhang1, Michael T. McManus3, Ophir D. Klein2,4 and Brad A. Amendt1,5,‡ SUMMARY The mouse incisor is a remarkable tooth that grows throughout the animal’s lifetime. This continuous renewal is fueled by adult epithelial stem cells that give rise to ameloblasts, which generate enamel, and little is known about the function of microRNAs in this process. Here, we describe the role of a novel Pitx2:miR-200c/141:noggin regulatory pathway in dental epithelial cell differentiation. miR-200c repressed noggin, an antagonist of Bmp signaling. Pitx2 expression caused an upregulation of miR-200c and chromatin immunoprecipitation assays revealed endogenous Pitx2 binding to the miR-200c/141 promoter. A positive-feedback loop was discovered between miR-200c and Bmp signaling. miR-200c/141 induced expression of E-cadherin and the dental epithelial cell differentiation marker amelogenin. In addition, miR-203 expression was activated by endogenous Pitx2 and targeted the Bmp antagonist Bmper to further regulate Bmp signaling. miR-200c/141 knockout mice showed defects in enamel formation, with decreased E-cadherin and amelogenin expression and increased noggin expression. Our in vivo and in vitro studies reveal a multistep transcriptional program involving the Pitx2:miR-200c/141:noggin regulatory pathway that is important in epithelial cell differentiation and tooth development. -
Embryonic Regeneration by Relocalization of the Spemann
Embryonic regeneration by relocalization of the PNAS PLUS Spemann organizer during twinning in Xenopus Yuki Moriyamaa,b,1 and Edward M. De Robertisa,b,2 aHoward Hughes Medical Institute, University of California, Los Angeles, CA 90095; and bDepartment of Biological Chemistry, David Geffen School of Medicine, University of California, Los Angeles, CA 90095-1662 Contributed by Edward M. De Robertis, April 3, 2018 (sent for review February 16, 2018; reviewed by Makoto Asashima, Atsushi Suzuki, and Naoto Ueno) The formation of identical twins from a single egg has fascinated side of the embryo in regularly cleaving embryos (9). The op- developmental biologists for a very long time. Previous work had posite, darker side of the embryo gives rise to the ventral (belly) shown that Xenopus blastulae bisected along the dorsal–ventral side. The displacement of egg cytoplasmic determinants along (D-V) midline (i.e., the sagittal plane) could generate twins but at microtubules toward the dorsal side triggers an early Wnt signal very low frequencies. Here, we have improved this method by (10), which is responsible for localizing the subsequent formation using an eyelash knife and changing saline solutions, reaching of the Spemann organizer signaling center in the marginal zone frequencies of twinning of 50% or more. This allowed mechanistic at the gastrula stage. The Spemann organizer is a tissue that analysis of the twinning process. We unexpectedly observed that secretes a mixture of growth factor antagonists, such as Chordin, the epidermis of the resulting twins was asymmetrically pig- Noggin, Follistatin, Cerberus, Frzb1, and Dickkopf, which are mented at the tailbud stage of regenerating tadpoles. -
Early Formation of the Müllerian Duct Is Regulated by Sequential Actions Of
© 2016. Published by The Company of Biologists Ltd | Development (2016) 143, 3549-3559 doi:10.1242/dev.137067 RESEARCH ARTICLE Early formation of the Müllerian duct is regulated by sequential actions of BMP/Pax2 and FGF/Lim1 signaling Yuji Atsuta1,* and Yoshiko Takahashi1,2,‡ ABSTRACT and MD form in close proximity, suggesting the possibility of The Müllerian duct (MD) and Wolffian duct (WD) are embryonic reciprocal interactions. tubular tissues giving rise to female and male reproductive tracts, In humans, approximately 3% of births are accompanied by respectively. In amniote embryos, both MD and WD emerge in both female reproductive tract-related disorders, including the Müllerian sexes, but subsequently degenerate in the males and females, aplasia, a congenital loss of the uterus and vagina (Ayers et al., respectively. Here, by using MD-specific gene manipulations in 2015; Kobayashi and Behringer, 2003; Layman, 2013; Sandbacka chicken embryos, we identify the molecular and cellular mechanisms et al., 2013). To understand how these disorders arise, it is important that link early MD specification to tubular invagination. Early (pre-) to delineate the mechanisms of MD formation. specification of MD precursors in the coelomic epithelium requires During embryonic development in both sexes, the MD arises BMP signaling and its downstream target Pax2 in a WD-independent from the lateral plate-derived coelomic epithelium (CE). The process. Subsequently, the BMP/Pax2 axis induces Lim1 processes of MD development can be divided into distinct phases: expression, a hallmark of MD specification, for which FGF/ERK and initiation, invagination and extension (Orvis and Behringer, 2007). WD-derived signals are also required. -
The TGF-Β Family in the Reproductive Tract
Downloaded from http://cshperspectives.cshlp.org/ on September 25, 2021 - Published by Cold Spring Harbor Laboratory Press The TGF-b Family in the Reproductive Tract Diana Monsivais,1,2 Martin M. Matzuk,1,2,3,4,5 and Stephanie A. Pangas1,2,3 1Department of Pathology and Immunology, Baylor College of Medicine, Houston, Texas 77030 2Center for Drug Discovery, Baylor College of Medicine, Houston, Texas 77030 3Department of Molecular and Cellular Biology, Baylor College of Medicine Houston, Texas 77030 4Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, Texas 77030 5Department of Pharmacology, Baylor College of Medicine, Houston, Texas 77030 Correspondence: [email protected]; [email protected] The transforming growth factor b (TGF-b) family has a profound impact on the reproductive function of various organisms. In this review, we discuss how highly conserved members of the TGF-b family influence the reproductive function across several species. We briefly discuss how TGF-b-related proteins balance germ-cell proliferation and differentiation as well as dauer entry and exit in Caenorhabditis elegans. In Drosophila melanogaster, TGF-b- related proteins maintain germ stem-cell identity and eggshell patterning. We then provide an in-depth analysis of landmark studies performed using transgenic mouse models and discuss how these data have uncovered basic developmental aspects of male and female reproductive development. In particular, we discuss the roles of the various TGF-b family ligands and receptors in primordial germ-cell development, sexual differentiation, and gonadal cell development. We also discuss how mutant mouse studies showed the contri- bution of TGF-b family signaling to embryonic and postnatal testis and ovarian development. -
Repair of Ultraviolet Irradiation Damage to a Cytoplasmic
Proc. Nat. Acad. Sci. USA Vol. 72, No. 4, pp. 1235-1239, April 1975 Repair of Ultraviolet Irradiation Damage to a Cytoplasmic Component Required for Neural Induction in the Amphibian Egg (cortex/vegetal hemisphere/gray crescent/dorsal lip/gastrulation) HAE-MOON CHUNG AND GEORGE M. MALACINSKI Department of Zoology, Indiana University, Bloomington, Ind. 47401 Communicated by Robert Briggs, January 2, 1975 ABSTRACT Localized ultraviolet irradiation of the am- In order to gain direct insight into whether an ultraviolet phibian egg destroys a cytoplasmic component that is sensitive component(s) localized in the egg cytoplasm prior required for neural induction. Destruction of that com- ponent severely diminishes the inducing capacity of the to first cleavage division is actually involved in neural dorsal lip at gastrulation, as determined by embryological induction, the following question was posed: Does regional assays. Repair of the ultraviolet lesion can be achieved by UV damage to the egg affect the subsequent inducing capacity replacing the dorsal lip of the irradiated embyro with a of the dorsal lip during gastrulation? By assaying for inducing lip from an unirradiated embryo. capacity of dorsal lips from irradiated embryos and replacing Various types of analyses have established that components the dorsal lips of irradiated embryos with normal lips it was of the amphibian egg cytoplasm influence the pattern of early possible to conclude that UV does indeed damage a localized morphogenesis (see ref. 1 for a review). One of the most component of the egg cytoplasm that is necessary for neural conveniently demonstrated, yet most incompletely under- morphogenesis. stood, cytoplasmic components in the amphibian egg is the MATERlALS AND METHODS gray crescent.