DOCSLIB.ORG

In Vivo Evidence That BMP Signaling Is Necessary for Apoptosis in the Mouse Limb

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
In Vivo Evidence That BMP Signaling Is Necessary for Apoptosis in the Mouse Limb Developmental Biology 249, 108–120 (2002) doi:10.1006/dbio.2002.0752 In Vivo Evidence That BMP Signaling Is Necessary for Apoptosis in the Mouse Limb Udayan Guha,*,†,1 William A. Gomes,* Tatsuya Kobayashi,‡ Richard G. Pestell,† and John A. Kessler§ *Department of Neuroscience, Albert Einstein College of Medicine, Bronx, New York 10461; ‡Endocrine Unit, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts 02115; †Division of Hormone-Dependant Tumor Biology, The Albert Einstein Cancer Center, Departments of Medicine, Developmental, and Molecular Biology, Albert Einstein College of Medicine, Bronx, New York 10461; and §Department of Neurology, Northwestern University Medical School, Chicago, Illinois 60611 To determine the role of Bone morphogenetic protein (BMP) signaling in murine limb development in vivo, the keratin 14 promoter was used to drive expression of the BMP antagonist Noggin in transgenic mice. Phosphorylation and nuclear translocation of Smad1/5 were dramatically reduced in limbs of the transgenic animals, confirming the inhibition of BMP signaling. These mice developed extensive limb soft tissue syndactyly and postaxial polydactyly. Apoptosis in the developing limb necrotic zones was reduced with incomplete regression of the interdigital tissue. The postaxial extra digit is also consistent with a role for BMPs in regulating apoptosis. Furthermore, there was persistent expression of Fgf8, suggesting a delay in the regression of the AER. However, Msx1 and Msx2 expression was unchanged in these transgenic mice, implying that induction of these genes is not essential for mediating BMP-induced interdigital apoptosis in mice. These abnormalities were rescued by coexpressing BMP4 under the same promoter in double transgenic mice, suggesting that the limb abnormalities are a direct effect of inhibiting BMP signaling. © 2002 Elsevier Science (USA) Key Words: BMP; Noggin; limb development; apoptosis; Msx; Hox; FGF8; keratin 14. INTRODUCTION oping vertebrate limb is also sculpted by programmed cell death of mesenchymal cells at the anterior and posterior Vertebrate limb buds originate from the embryonic flank margins of the limb bud (anterior necrotic zone, ANZ; and with contributions from both the lateral plate and the posterior necrotic zone, PNZ) and in the interdigital ne- somatic mesoderm. Bones, cartilage, and tendons in the crotic zones (INZ) between the developing digits. limb are derived from the lateral plate mesoderm, while The BMPs are a large family of secreted ligands within muscles, vasculature, and nerves are derivatives of the the TGF␤ superfamily that play essential roles in embry- somatic mesoderm. Early limb bud development is regu- onic development (Hogan, 1996). BMP signaling is received lated by epithelial–mesenchymal interactions between a by two types of serine threonine kinase receptors, type I highly specialized pseudostratified columnar epithelium at (BMPRI) and type II (BMPRII). On ligand binding, the type II the tip of the limb bud, called the apical ectodermal ridge receptor phosphorylates a type I recptor which then triggers (AER), and mesenchymal cells underlying the AER and at an intracellular signaling cascade involving proteins of the the posterior margin of the limb bud, in a region called the SMAD family. BMP2 and BMP4, members of the drosophila zone of polarizing activity (ZPA) (Dudley and Tabin, 2000). decapentaplegic (dpp) family of the BMPs, and BMP7 (also Mesenchymal cells aggregate to form prechondrogenic con- known as OP-1) are expressed in the undifferentiated mes- densations that subsequently ossify to form the bony skel- enchyme, interdigital mesenchyme, and the AER of the eton of the limb (Pizette and Niswander, 2001). The devel- developing limb (Laufer et al., 1997; Lyons et al., 1995). BMP receptors also show specific temporal and spatial 1 To whom correspondence should be addressed. Fax: (718) 430- patterns of expression in developing limbs in the mouse and 8674. E-mail: [email protected]. chick (Dewulf et al., 1995; Yi et al., 2000; Zou et al., 1997). 0012-1606/02 $35.00 © 2002 Elsevier Science (USA) 108 All rights reserved. BMP Signaling in Murine Limb Development 109 FIG. 1. Generation of K14-Noggin transgenic mice. (A) Diagram of the linearized transgene construct that was injected. (B) Southern blot analysis of genomic DNA from the tail digested with KpnI and probed with random primed ␣P32-labeled Noggin probe. The 5-kb band is the transgene, and the lower band is the endogenous gene. (C) Noggin protein is overexpressed in the transgenic adult back skin. GDI has been used as loading control. (D) Whole-mount in situ hybridization for Noggin (a, b) and Bmp4 (c, d) expression of E12.5 embryos shows that both Noggin and Bmp4 are misexpressed in all the limbs of transgenic (b, d) compared with wild type embryos (a, c). FL, forelimb; HL, hindlimb; W, whisker. FIG. 2. BMP signaling is reduced in K14-Noggin limbs. P-Smad1/5 immunoreactivity is significantly reduced in K14-Noggin interdigital mesenchyme (B) compared with the wild type (A). BMP functions are antagonized by a large number of se- others) that bind BMPs extracellularly thereby preventing creted proteins, such as Noggin, Chordin, Follistatin, and binding of the BMPs to their receptors. Noggin (Brunet et the DAN family members (Gremlin, Cerberus, DAN, and al., 1998; Capdevila and Johnson, 1998; Pizette and Niswan- © 2002 Elsevier Science (USA). All rights reserved. 110 Guha et al. FIG. 3. K14-Noggin mice have abnormalities in limb development. (A) Scanning EM micrograph of the ventral side of E14.5 forelimb (a, b) and hindlimb (c, d); anterior is to the left. (B) Newborn forelimbs dorsal side (a, c), ventral side (e), and hindlimbs dorsal side (b, d) and ventral side (f). (C) Forelimbs (a–c) and hindlimbs (d–f) of 1-month-old mice in Fvb inbred background (c, f) and Fvb ϫ CB6F1, outbred background (a, b, d, e) show distinct abnormalities in the transgenic (b, c, e, f). (D) Alizarin red and Alcian blue staining of postnatal day 2 (P2) forelimb shows proportionally shortened digits and the postaxial extra digit (VЈ) in the transgenic animals. der, 1999), Gremlin (Capdevila et al., 1999; Merino et al., 2000). BMPs also mediate interdigital cell death in the 1999b), DAN (Pearce et al., 1999), Chordin (Francis-West et chick (Kawakami et al., 1996; Macias et al., 1997; Yokouchi al., 1999), Follistatin (Merino et al., 1999a), and Drm et al., 1996; Zou and Niswander, 1996) and induce cell (Pearce et al., 1999) are all expressed in the developing limb. death in murine interdigital explant cultures (Tang et al., BMP signaling is necessary for the proliferation and differ- 2000). However, a role for the BMPs in murine interdigital entiation of precartilaginous mesenchyme of the phalangeal apoptosis in vivo has not been established. Homozygous region in mice (Baur et al., 2000; Yi et al., 2000) and also deletion of Bmp2 or Bmp4 causes lethality in early devel- chondrocyte differentiation in the chick (Duprez et al., opment, so their role in limb apoptosis has not been studied 1996; Macias et al., 1997; Merino et al., 1998). BMPs in mice (Winnier et al., 1995; Zhang and Bradley, 1996). regulate the growth and regression of the AER in the chick Bmp7 knockout mice exhibit mild patterning defects in the (Ganan et al., 1998; Pizette and Niswander, 2000) and limb in the form of preaxial polydactyly (Luo et al., 1995). specify anteroposterior digital identity (Dahn and Fallon, Since BMP2, BMP4, and BMP7 are all expressed in the © 2002 Elsevier Science (USA). All rights reserved. BMP Signaling in Murine Limb Development 111 interdigital mesenchyme before and during the onset of Western Blot Analysis interdigital apoptosis, loss of the ligand in single knockouts Transgene expression in the adult was determined by Western is also likely to be compensated by other members of the blot analysis of lysates prepared from adult back skin or embryonic family. Similarly, Bmpr1a knockout mice die on embryonic limb homogenates with a rat monoclonal Noggin antibody, RP57- day 9.5 (E9.5) of gestation (Mishina et al., 1995). Recently, a 16, a gift from Regeneron pharmaceuticals. To verify equal loading, conditional mutant of Bmpr1a in the limb demonstrated polyclonal anti-guanine nucleotide dissociation inhibitor (GDI) (a severe limb phenotype due to interference with the forma- gift from Dr. Perry Bickel, Washington University, St. Louis, MO) tion of the AER and dorsoventral patterning of the limb, but was used. a role of BMP signaling in limb necrotic zone apoptosis was not apparent (Ahn et al., 2001). Bmpr1b knockout mice Analysis of Apoptosis show phalangeal defects, but there is no change in the Cell death was detected by vital dye staining with Nile blue apoptosis of autopodial elements (Yi et al., 2000), raising sulfate (Sigma N-5632) as previously described (Tone, 1983). questions about the proapoptotic role of the BMPs in Briefly, embryos were collected in cold phosphate-buffered saline mouse. (PBS), then incubated in prewarmed DMEM containing 0.001% In order to study the role of BMP signaling in limb Nile blue sulfate at 37°C for 1 h, washed in PBS for5hat4°C, and development in vivo, the keratin 14 (K14) promoter was photographed. Apoptotic cells were detected by TUNEL assay on used to drive expression of the BMP antagonist Noggin in 4% paraformaldehyde fixed serial cryosections of E13.5 and E14.5 transgenic mice. These mice were found to have extensive limbs by using the Apoptag–Rhodamine kit (Intergen, Purchase, soft tissue syndactyly in both the forelimb and hindlimb as NY) according to the manufacturer’s protocol. Activated caspase-3 was detected by Cleaved Caspase-3 (Asp175) Antibody (Cell Sig- well as postaxial polydactyly. There was decreased apopto- naling, Beverly, MA). sis in the necrotic zones in the developing limb leading to incomplete regression of the interdigital tissue and possibly a fate change in the region of the posterior necrotic zone to X-Ray Analysis and Skeleton Preparations an extra digit.
Load more

Recommended publications
  • Segmentation and Specification of the Drosophila Mesoderm
    Downloaded from genesdev.cshlp.org on September 25, 2021 - Published by Cold Spring Harbor Laboratory Press Segmentation and specification of the Drosophila mesoderm Natalia Azpiazu, 1,3 Peter A. Lawrence, 2 Jean-Paul Vincent, 2 and Manfred Frasch 1'4 1Brookdale Center for Molecular Biology, Mount Sinai School of Medicine, New York, New York 10029 USA; 2Medical Research Council Laboratory of Molecular Biology, Cambridge CB2 2QH, UK Patterning of the developing mesoderm establishes primordia of the visceral, somatic, and cardiac tissues at defined anteroposterior and dorsoventral positions in each segment. Here we examine the mechanisms that locate and determine these primordia. We focus on the regulation of two mesodermal genes: bagpipe (hap), which defines the anlagen of the visceral musculature of the midgut, and serpent (srp), which marks the anlagen of the fat body. These two genes are activated in specific groups of mesodermal cells in the anterior portions of each parasegment. Other genes mark the anlagen of the cardiac and somatic mesoderm and these are expressed mainly in cells derived from posterior portions of each parasegment. Thus the parasegments appear to be subdivided, at least with respect to these genes, a subdivision that depends on pair-rule genes such as even-skipped (eve). We show with genetic mosaics that eve acts autonomously within the mesoderm. We also show that hedgehog (hh) and wingless (wg) mediate pair-rule gene functions in the mesoderm, probably partly by acting within the mesoderm and partly by inductive signaling from the ectoderm, hh is required for the normal activation of hap and srp in anterior portions of each parasegment, whereas wg is required to suppress bap and srp expression in posterior portions.
    [Show full text]
  • Mesoderm Induction and the Control of Gastrulation in Xenopus Laevis:The
    Development 108, 229-238 (1990) 229 Printed in Great Britain ©The Company of Biologists Limited 1990 Mesoderm induction and the control of gastrulation in Xenopus laevis: the roles of fibronectin and integrins J. C. SMITH1, K. SYMESH, R. O. HYNES2'3 and D. DeSIMONE3* ' Laboratory of Embryogenesis, National Institute for Medical Research, The Ridgeway, Mill Hill, London NW71AA, UK ^Howard Hughes Medical Institute and ^Center for Cancer Research, Department of Biology, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, USA * Present address: University of Virginia, Health Sciences Center, Department of Anatomy and Cell Biology, Box 439, School of Medicine, Charlottesville, VA 22908, USA t Present address: Department of Cell and Molecular Biology, 385 LSA, University of California, Berkeley, CA 94720, USA Summary Exposure of isolated Xenopus animal pole ectoderm to diated cell migration is not required for convergent the XTC mesoderm-inducing factor (XTC-MIF) causes extension. the tissue to undergo gastrulation-like movements. In We have investigated the molecular basis of XTC- this paper, we take advantage of this observation to MIF-induced gastrulation-like movements by measuring investigate the control of various aspects of gastrulation rates of synthesis of fibronectin and of the integrin f}y in Xenopus. chain in induced and control explants. No significant Blastomcres derived from induced animal pole regions differences were observed, and this suggests that gastru- are able, like marginal zone cells, but unlike control lation is not initiated simply by control of synthesis of animal pole blastomeres, to spread and migrate on a these molecules. In future work, we intend to investigate fibronectin-coated surface.
    [Show full text]
  • Understanding Paraxial Mesoderm Development and Sclerotome Specification for Skeletal Repair Shoichiro Tani 1,2, Ung-Il Chung2,3, Shinsuke Ohba4 and Hironori Hojo2,3
    Tani et al. Experimental & Molecular Medicine (2020) 52:1166–1177 https://doi.org/10.1038/s12276-020-0482-1 Experimental & Molecular Medicine REVIEW ARTICLE Open Access Understanding paraxial mesoderm development and sclerotome specification for skeletal repair Shoichiro Tani 1,2, Ung-il Chung2,3, Shinsuke Ohba4 and Hironori Hojo2,3 Abstract Pluripotent stem cells (PSCs) are attractive regenerative therapy tools for skeletal tissues. However, a deep understanding of skeletal development is required in order to model this development with PSCs, and for the application of PSCs in clinical settings. Skeletal tissues originate from three types of cell populations: the paraxial mesoderm, lateral plate mesoderm, and neural crest. The paraxial mesoderm gives rise to the sclerotome mainly through somitogenesis. In this process, key developmental processes, including initiation of the segmentation clock, formation of the determination front, and the mesenchymal–epithelial transition, are sequentially coordinated. The sclerotome further forms vertebral columns and contributes to various other tissues, such as tendons, vessels (including the dorsal aorta), and even meninges. To understand the molecular mechanisms underlying these developmental processes, extensive studies have been conducted. These studies have demonstrated that a gradient of activities involving multiple signaling pathways specify the embryonic axis and induce cell-type-specific master transcription factors in a spatiotemporal manner. Moreover, applying the knowledge of mesoderm development, researchers have attempted to recapitulate the in vivo development processes in in vitro settings, using mouse and human PSCs. In this review, we summarize the state-of-the-art understanding of mesoderm development and in vitro modeling of mesoderm development using PSCs. We also discuss future perspectives on the use of PSCs to generate skeletal tissues for basic research and clinical applications.
    [Show full text]
  • Sonic Hedgehog a Neural Tube Anti-Apoptotic Factor 4013 Other Side of the Neural Plate, Remaining in Contact with Midline Cells, RESULTS Was Used As a Control
    Development 128, 4011-4020 (2001) 4011 Printed in Great Britain © The Company of Biologists Limited 2001 DEV2740 Anti-apoptotic role of Sonic hedgehog protein at the early stages of nervous system organogenesis Jean-Baptiste Charrier, Françoise Lapointe, Nicole M. Le Douarin and Marie-Aimée Teillet* Institut d’Embryologie Cellulaire et Moléculaire, CNRS FRE2160, 49bis Avenue de la Belle Gabrielle, 94736 Nogent-sur-Marne Cedex, France *Author for correspondence (e-mail: [email protected]) Accepted 19 July 2001 SUMMARY In vertebrates the neural tube, like most of the embryonic notochord or a floor plate fragment in its vicinity. The organs, shows discreet areas of programmed cell death at neural tube can also be recovered by transplanting it into several stages during development. In the chick embryo, a stage-matched chick embryo having one of these cell death is dramatically increased in the developing structures. In addition, cells engineered to produce Sonic nervous system and other tissues when the midline cells, hedgehog protein (SHH) can mimic the effect of the notochord and floor plate, are prevented from forming by notochord and floor plate cells in in situ grafts and excision of the axial-paraxial hinge (APH), i.e. caudal transplantation experiments. SHH can thus counteract a Hensen’s node and rostral primitive streak, at the 6-somite built-in cell death program and thereby contribute to organ stage (Charrier, J. B., Teillet, M.-A., Lapointe, F. and Le morphogenesis, in particular in the central nervous system. Douarin, N. M. (1999). Development 126, 4771-4783). In this paper we demonstrate that one day after APH excision, Key words: Apoptosis, Avian embryo, Cell death, Cell survival, when dramatic apoptosis is already present in the neural Floor plate, Notochord, Quail/chick, Shh, Somite, Neural tube, tube, the latter can be rescued from death by grafting a Spinal cord INTRODUCTION generally induces an inflammatory response.
    [Show full text]
  • The Derivatives of Three-Layered Embryo (Germ Layers)
    HUMANHUMAN EMBRYOLOGYEMBRYOLOGY Department of Histology and Embryology Jilin University ChapterChapter 22 GeneralGeneral EmbryologyEmbryology FourthFourth week:week: TheThe derivativesderivatives ofof trilaminartrilaminar germgerm discdisc Dorsal side of the germ disc. At the beginning of the third week of development, the ectodermal germ layer has the shape of a disc that is broader in the cephalic than the caudal region. Cross section shows formation of trilaminar germ disc Primitive pit Drawing of a sagittal section through a 17-day embryo. The most cranial portion of the definitive notochord has formed. ectoderm Schematic view showing the definitive notochord. horizon =ectoderm hillside fields =neural plate mountain peaks =neural folds Cave sinks into mountain =neural tube valley =neural groove 7.1 Derivatives of the Ectodermal Germ Layer 1) Formation of neural tube Notochord induces the overlying ectoderm to thicken and form the neural plate. Cross section Animation of formation of neural plate When notochord is forming, primitive streak is shorten. At meanwhile, neural plate is induced to form cephalic to caudal end, following formation of notochord. By the end of 3rd week, neural folds and neural groove are formed. Neural folds fuse in the midline, beginning in cervical region and Cross section proceeding cranially and caudally. Neural tube is formed & invade into the embryo body. A. Dorsal view of a human embryo at approximately day 22. B. Dorsal view of a human embryo at approximately day 23. The nervous system is in connection with the amniotic cavity through the cranial and caudal neuropores. Cranial/anterior neuropore Neural fold heart Neural groove endoderm caudal/posterior neuropore A.
    [Show full text]
  • Differential Genetic Mutations of Ectoderm, Mesoderm, And
    Gao et al. Cancer Cell Int (2020) 20:595 https://doi.org/10.1186/s12935-020-01678-x Cancer Cell International PRIMARY RESEARCH Open Access Diferential genetic mutations of ectoderm, mesoderm, and endoderm-derived tumors in TCGA database Xingjie Gao1,2*, Xiaoteng Cui1,2,3, Xinxin Zhang1,2, Chunyan Zhao1,2, Nan Zhang1,2, Yan Zhao1,2, Yuanyuan Ren1,2, Chao Su1,2, Lin Ge1,2, Shaoyuan Wu1,2 and Jie Yang1,2* Abstract Background: In terms of biological behavior, gene regulation, or signaling pathways, there is a certain similarity between tumorigenesis and embryonic development of humans. Three germ layer structure exhibits the distinct abil- ity to form specifc tissues and organs. Methods: The present study set out to investigate the genetic mutation characteristics of germ layer diferentiation- related genes using the tumor cases of the cancer genome atlas (TCGA) database. Results: These tumor samples were divided into three groups, including the ectoderm, mesoderm, and endoderm. Children cases less than 9 years old accounted for a larger proportion for the cases in the ectoderm and mesoderm groups; whereas the middle-aged and elderly individuals (from 50 to 89 years old) were more susceptible to tumors of endoderm. There was a better prognosis for the cases of mesoderm, especially the male with the race of White, compared with the other groups. A missense mutation was frequently detected for the cases of ectoderm and endo- derm, while deletion mutation was common for that of mesoderm. We could not identify the ectoderm, mesoderm, or endoderm-specifc mutated genes or variants with high mutation frequency.
    [Show full text]
  • Programmed Cell Death in the Developing Limb
    Int. J. Dev. Biol. 46: 871-876 (2002) Programmed cell death in the developing limb VANESSA ZUZARTE-LUÍS and JUAN M. HURLÉ* Departamento de Anatomía y Biología Celular, Facultad de Medicina, Universidad de Cantabria, Santander, Spain ABSTRACT The sculpturing of shape in the developing limb together with the regression of the tail in anuran tadpoles constitute, perhaps, the most paradigmatic processes of programmed cell death. The study of these model systems has been of fundamental importance to support the idea that cell death is a physiological behavior of cells in multicellular organisms. Furthermore, different experimental approaches, including comparative analyses of the pattern of cell death in different avian species (i.e. chick interdigits versus duck interdigital webs) and in chick mutants with different limb phenotypes, provided the first evidence for the occurrence of a genetic program underlying the control of cell death. Two well known research groups in the field of limb development, the USA group headed first by John Saunders and next by John Fallon and the group of Donald Ede and Richard Hinchliffe in the U.K. provided a remarkable contribution to this topic. In spite of the historical importance of the developing limb in establishing the concept of programmed cell death, this model system of tissue regression has been largely neglected in recent studies devoted to the analysis of the molecular control of self-induced cell death (apoptosis). However, a considerable amount of information concerning this topic has been obtained in the last few years. Here we will review current information on the control of limb programmed cell death in an attempt to stimulate further molecular studies of this process of tissue regression.
    [Show full text]
  • Functional Morphology of the Cardiac Jelly in the Tubular Heart of Vertebrate Embryos
    Review Functional Morphology of the Cardiac Jelly in the Tubular Heart of Vertebrate Embryos Jörg Männer 1,*,† and Talat Mesud Yelbuz 2,† 1 Group Cardio‐Embryology, Institute of Anatomy and Embryology UMG, Georg‐August‐University Goettingen, D‐37075 Goettingen, Germany; [email protected] 2 Department of Cardiac Sciences, King Abdulaziz Cardiac Center, Section of Pediatric Cardiology, King Abdulaziz Medical City, Ministry of National Guard Health Affairs, Riyadh 11426, Saudi Arabia; [email protected] * Correspondence: [email protected]; Tel.: +49‐551‐39‐7032 † This work is dedicated to the memory of our academic mentors Gerd Steding (1936–2011) and Armin Wessel (1946–2011). Received: 29 January 2019; Accepted: 21 February 2019; Published: 27 February 2019 Abstract: The early embryonic heart is a multi‐layered tube consisting of (1) an outer myocardial tube; (2) an inner endocardial tube; and (3) an extracellular matrix layer interposed between the myocardium and endocardium, called “cardiac jelly” (CJ). During the past decades, research on CJ has mainly focused on its molecular and cellular biological aspects. This review focuses on the morphological and biomechanical aspects of CJ. Special attention is given to (1) the spatial distribution and fiber architecture of CJ; (2) the morphological dynamics of CJ during the cardiac cycle; and (3) the removal/remodeling of CJ during advanced heart looping stages, which leads to the formation of ventricular trabeculations and endocardial cushions. CJ acts as a hydraulic skeleton, displaying striking structural and functional similarities with the mesoglea of jellyfish. CJ not only represents a filler substance, facilitating end‐systolic occlusion of the embryonic heart lumen.
    [Show full text]
  • Conversion of Presumptive Ectoderm to Mesoderm in the Chick by C
    335 CONVERSION OF PRESUMPTIVE ECTODERM TO MESODERM IN THE CHICK BY C. H. WADDINGTON,1 M.A. AND JEAN TAYLOR, B.A. From the Strangeways Laboratory and Sub-Department of Experimental Zoology, Cambridge (Received 10 November 1936) (With One Plate) INTRODUCTION THE greater part of descriptive embryology is based on the concept of the three germ-layers—ectoderm, mesoderm and endoderm. As we acquire more information about the physiology of development, it is natural to ask whether the same concept is as fundamental for a consideration of individual development as it is for com- parative morphology. The investigations on the Amphibia have already provided a negative answer for that group. Mangold (1925), in a review on the subject, pointed out that presumptive ectoderm could be caused to undergo differentiation into endodermal organs or mesodermal organs. More recently, Lopashov (1935) and Tondury (1936) have shown that mesoderm can become ectoderm. Only the heavy yolk-laden endoderm cannot be changed into anything else, a disability which is probably not an expression of any fundamental determination but rather an adventitious circumstance depending on the presence of large masses of inactive yolk. Mangold describes two ways in which ectoderm can-become converted into mesoderm; either the presumptive ectoderm can be grafted into the blastopore or it can be inserted directly into the blastocoel cavity. In the first case, it takes part in the gastrulation movements of the host, but the fact that mesodermal organs are also formed by grafts made in the second way show that these movements are not essential for subsequent mesodermal differentiation.
    [Show full text]
  • Embryology and Teratology in the Curricula of Healthcare Courses
    ANATOMICAL EDUCATION Eur. J. Anat. 21 (1): 77-91 (2017) Embryology and Teratology in the Curricula of Healthcare Courses Bernard J. Moxham 1, Hana Brichova 2, Elpida Emmanouil-Nikoloussi 3, Andy R.M. Chirculescu 4 1Cardiff School of Biosciences, Cardiff University, Museum Avenue, Cardiff CF10 3AX, Wales, United Kingdom and Department of Anatomy, St. George’s University, St George, Grenada, 2First Faculty of Medicine, Institute of Histology and Embryology, Charles University Prague, Albertov 4, 128 01 Prague 2, Czech Republic and Second Medical Facul- ty, Institute of Histology and Embryology, Charles University Prague, V Úvalu 84, 150 00 Prague 5 , Czech Republic, 3The School of Medicine, European University Cyprus, 6 Diogenous str, 2404 Engomi, P.O.Box 22006, 1516 Nicosia, Cyprus , 4Department of Morphological Sciences, Division of Anatomy, Faculty of Medicine, C. Davila University, Bucharest, Romania SUMMARY Key words: Anatomy – Embryology – Education – Syllabus – Medical – Dental – Healthcare Significant changes are occurring worldwide in courses for healthcare studies, including medicine INTRODUCTION and dentistry. Critical evaluation of the place, tim- ing, and content of components that can be collec- Embryology is a sub-discipline of developmental tively grouped as the anatomical sciences has biology that relates to life before birth. Teratology however yet to be adequately undertaken. Surveys (τέρατος (teratos) meaning ‘monster’ or ‘marvel’) of teaching hours for embryology in US and UK relates to abnormal development and congenital medical courses clearly demonstrate that a dra- abnormalities (i.e. morphofunctional impairments). matic decline in the importance of the subject is in Embryological studies are concerned essentially progress, in terms of both a decrease in the num- with the laws and mechanisms associated with ber of hours allocated within the medical course normal development (ontogenesis) from the stage and in relation to changes in pedagogic methodol- of the ovum until parturition and the end of intra- ogies.
    [Show full text]
  • Programmed Cell Death in the Developing Somites Is Promoted By
    Developmental Biology 228, 326–336 (2000) doi:10.1006/dbio.2000.9948, available online at http://www.idealibrary.com on View metadata, citation and similar papers at core.ac.uk brought to you by CORE Programmed Cell Death in the Developing Somitesprovided by Elsevier - Publisher Connector Is Promoted by Nerve Growth Factor via Its p75NTR Receptor Marı´a L. Cotrina, Maritza Gonza´lez-Hoyuela, Julio A. Barbas, and Alfredo Rodrı´guez-Te´bar1 Instituto Cajal de Neurobiologı´a, CSIC, Avenida Doctor Arce, 37, E-28002 Madrid, Spain Neurotrophins control neuron number during development by promoting the generation and survival of neurons and by regulating programmed neuronal death. In the latter case, the cell death induced by nerve growth factor (NGF) in the developing chick retina is mediated by p75NTR, the common neurotrophin receptor (J. M. Frade, A. Rodriguez-Tebar, and Y.-A. Barde, 1996, Nature 383, 166–168). Here we show that NGF also induces the programmed death of paraxial mesoderm cells in the developing somites. Both NGF and p75NTR are expressed in the somites of chick embryos at the time and the place of programmed cell death. Moreover, neutralizing the activity of endogenous NGF with a specific blocking antibody, or antagonizing NGF binding to p75NTR by the application of human NT-4/5, reduces the levels of apoptotic cell death in both the sclerotome and the dermamyotome by about 50 and 70%, respectively. Previous data have shown that Sonic hedgehog is necessary for the survival of differentiated somite cells. Consistent with this, Sonic hedgehog induces a decrease of NGF mRNA in somite explant cultures, thus showing the antagonistic effect of NGF and Sonic hedgehog with respect to somite cell survival.
    [Show full text]
  • Functional Morphology of the Cardiac Jelly in the Tubular
    Preprints (www.preprints.org) | NOT PEER-REVIEWED | Posted: 30 January 2019 doi:10.20944/preprints201901.0312.v1 Peer-reviewed version available at J. Cardiovasc. Dev. Dis. 2019, 6, 12; doi:10.3390/jcdd6010012 1 Review 2 Functional Morphology of the Cardiac Jelly in the 3 Tubular Heart of Vertebrate Embryos 4 Jörg Männer 1,* and Talat Mesud Yelbuz 2 5 1 Group Cardio-Embryology, Institute of Anatomy and Embryology UMG, Georg-August-University 6 Goettingen, D-37075 Goettingen, Germany; [email protected] 7 2 Department of Cardiac Sciences, King Abdulaziz Cardiac Center, Section of Pediatric Cardiology, King 8 Abdulaziz Medical City, Ministry of National Guard Health Affairs; Riyadh, Kingdom of Saudi Arabia; 9 [email protected] 10 * Correspondence: [email protected]; Tel.: +49-551-39-7032 11 12 Abstract: The early embryonic heart is a multi-layered tube consisting of (1) an 13 outer myocardial tube; (2) an inner endocardial tube; and (3) an extracellular 14 matrix layer interposed between myocardium and endocardium, called “cardiac 15 jelly” (CJ). During the past decades, research on CJ has mainly focused on its 16 molecular and cell biological aspects. This review focuses on the morphological 17 and biomechanical aspects of CJ. Special attention is given to (1) the spatial 18 distribution and fiber architecture of CJ; (2) the morphological dynamics of CJ 19 during the cardiac cycle; and (3) the removal/remodeling of CJ during advanced 20 heart looping stages, which leads to the formation of ventricular trabeculations 21 and endocardial cushions. CJ acts as a hydraulic skeleton displaying striking 22 structural and functional similarities with the mesoglea of jellyfish.
    [Show full text]