The Identification and Characterization of a Novel, Vertebrate Specific Gene, with Potential Roles in Human Cri Du Chat Syndrome

Total Page:16

File Type:pdf, Size:1020Kb

The Identification and Characterization of a Novel, Vertebrate Specific Gene, with Potential Roles in Human Cri Du Chat Syndrome IDENTIFICATION AND ANALYSIS OF THE NOVEL GUMBY GENE AND ITS VERTEBRATE SPECIFIC ROLES IN THE MOUSE by ELENA RIVKIN A thesis submitted in conformity with requirements for the degree of Doctor of Philosophy. Graduate Department of Molecular Genetics University of Toronto © Copyright by Elena Rivkin, 2010 Identification and analysis of the novel gumby gene and its vertebrate roles in the mouse Elena Rivkin Doctor of Philosophy Department of Molecular Genetics University of Toronto 2010 ABSTRACT Forward genetic screens in the mouse are contributing significantly to our understanding of basic mammalian development and human disease. In one such screen, our laboratory has identified the novel mouse gumby mutant, which affects the development of the neural and vascular systems. Here, I describe the characterization of the gumby mutant phenotype and the identification of its causative mutation in a novel, vertebrate-specific gene, which is one of the genes deleted in patients affected by Cri du Chat Syndrome that exhibit mental retardation and craniofacial deficits. Expression and phenotypic analyses revealed a requirement for the gumby gene in the facial nerve axon guidance and angiogenesis. Lately, it has become evident that many common mechanisms and molecules operate during neural and vascular development. My results suggest that the gumby gene is an attractive candidate for regulating both processes and its analysis in the future may help us understand how the navigational mechanisms for both systems are intertwined. ii My studies show that gumby is a cytoplasmic protein that is present in many embryonic and adult tissues. In yeast-two-hybrid assays gumby interacts with a member of the highly conserved Wnt pathway - Dishevelled 2 (Dvl2). In both Dvl2-/- and gumby homozygotes, the level of the cardiac neural crest cell marker Plexin2A is decreased. The three branches of the Wnt pathway have been shown to regulate a wide range of events during embryogenesis and adult homeostasis, and subsequently have been implicated in multiple human pathologies. Taken together my data suggest that gumby may be required for Wnt signaling in angiogenesis and/or facial nerve guidance. Given that Wnt signaling has been shown to play key roles in axon guidance, gumby and its roles in Wnt signaling may also contribute to the mental retardation seen in patients with Cri du Chat Syndrome. Thus, further analyses of molecular and biologic roles of gumby will provide important avenues for understanding the cell biology of human disease. iii ACKNOWLEDGEMENTS First and foremost, I would like to thank my supervisor Dr. Sabine Cordes for giving me the opportunity to work with her and for being a great mentor throughout this project. Without her guidance and persistent help, this dissertation would not be possible. I am truly grateful for my committee members, Dr. C. C Hui and Dr. Joseph Culotti who have made their support and assistance available in a number of ways, and whose advice has shaped this project tremendously. I would like to acknowledge my fellow lab members with whom I had the pleasure of working over the years. These include Stephanie Almeida, Michael Huynh, Dennis Kim, Teresa MacLean, Ryan Mui, Angela Sing, Kendra Sturgeon, and Joanna Yu. You have created a great research environment and I will remember and cherish you forever. Lastly, I would like to offer my eternal gratitude to my family and friends who offered me support and encouragement during the completion of this project. I am especially grateful to my wonderful husband and our little creation Julia, who mean the world to me, and constantly inspire me to work harder and to aim higher. iv TABLE OF CONTENTS Abstract...............................................................................................................................ii Acknowledgements............................................................................................................iv Table of contents.................................................................................................................v List of tables.......................................................................................................................ix List of figures......................................................................................................................x List of appendices.............................................................................................................xii Abbreviation key..............................................................................................................xiii 1.0 INTRODUCTION....................................................................................................... 1 1.1 Overview of work that has led to this project............................................................... 1 1.1.1 Forward genetic screen to identify cranial nerve mutations in the mouse..........1 1.2 Overview of vertebrate cranial nerves and their early development ............................ 8 1.2.1 The unique development of the facial cranial nerve.........................................12 1.2.1.1 Basic neuroanatomical development of facial cranial nerve .................... 12 1.2.1.2 Migration of facial branchiomotor neurons .............................................. 13 1.2.1.3 Axon guidance of facial cranial nerves..................................................... 15 1.3 Human cranial dysinnervation disorders .................................................................... 19 1.4 Cri du Chat Syndrome ................................................................................................ 21 1.5 Overview of Angiogenesis.......................................................................................... 22 1.5.1 VEGF/VEGFR signaling in vascular development ..........................................23 1.5.2 Notch signaling in angiogenesis .......................................................................25 1.5.3 Wnt signaling in vascular development............................................................27 1.5.3.1 Short summary of Wnt pathways.............................................................. 27 1.6 Common mechanisms of nerve and blood vessel development ................................. 35 1.6.1 Pathways with roles in facial nerve axon guidance and angiogenesis..............37 1.6.2 Pathways with roles in FBM migration and angiogenesis................................40 1.6.2.1 Neuropilins and VEGF ............................................................................. 40 1.6.2.2 Wnt signaling pathway ............................................................................. 41 1.6.3 Other axon guidance pathways with roles in cranial nerve development and...... angiogenesis.....................................................................................................43 1.6.3.1 Eph-Ephrins .............................................................................................. 43 1.6.3.2 Netrins and Unc5b .................................................................................... 45 1.6.3.2 Slits and Robos ......................................................................................... 46 1.7 Summary..................................................................................................................... 47 2.0 MATERIALS AND METHODS ............................................................................. 49 2.1 Mouse Manipulations.................................................................................................. 49 v 2.2 Embryos harvesting .................................................................................................... 49 2.3 Synthesis of first strand cDNA ................................................................................... 49 2.4 Mouse genotyping....................................................................................................... 49 2.4.1 Standard PCR assay ..........................................................................................50 2.5 Genetic mapping of the gumby mutation.................................................................... 50 2.5.1 Initial mapping done by other members of our laboratory ...............................50 2.5.2 Fine mapping of the gumby mutation ...............................................................50 2.5.3 Sequencing the genes within gumby critical interval........................................52 2.5.4 Sequencing Fam105b........................................................................................52 2.5.5 Genotyping the T285A mutation using ARMS-PCR analysis .........................53 2.6 Cloning of Fam105b................................................................................................... 54 2.6.1 Synthesis of first strand cDNA .........................................................................54 2.6.2 Cloning of Fam105b-pBluescript SKII.............................................................54 2.7 Histological Analysis.................................................................................................. 55 2.8 Northern Blot analysis .........................................................................................55 2.9 Apoptosis and Proliferation Assays............................................................................ 56 2.10 Whole-mount in situ hybridization (WISH) ............................................................. 56 2.10.1 Fam105b
Recommended publications
  • Embryology and Anatomy of Fetal Heart
    Prof. Saeed Abuel Makarem Dr. Jamila El Medany Objectives • By the end of this lecture the student should be able to: • Describe the formation, sit, union divisions of the of the heart tubes. • Describe the formation and fate of the sinus venosus. • Describe the partitioning of the common atrium and common ventricle. • Describe the partitioning of the truncus arteriosus. • List the most common cardiac anomalies. • The CVS is the first major system to function in the embryo. • The heart begins to beat at (22nd – 23rd ) days. • Blood flow begins during the beginning of the fourth week and can be visualized by Ultrasound Doppler Notochord: stimulates neural tube formation Somatic mesoderm Splanchnic mesoderm FORMATION OF THE HEART TUBE • The heart is the first functional organ to develop. • It develops from Splanchnic Mesoderm in the wall of the yolk sac (Cardiogenic Area): Cranial to the developing Mouth & Nervous system and Ventral to the developing Pericardial sac. • The heart primordium is first evident at day 18 (as an Angioplastic cords which soon canalize to form the 2 heart tubes). • As the Head Fold completed, the developing heart tubes change their position and become in the Ventral aspect of the embryo, Dorsal to the developing Pericardial sac. • . Development of the Heart tube • After Lateral Folding of the embryo, the 2 heart tubes approach each other and fuse to form a single Endocardial Heart tube within the pericardial sac. • Fusion of the two tubes occurs in a Craniocaudal direction. What is the • The heart tube grows faster than shape of the the pericardial sac, so it shows 5 alternate dilations separated by Heart Tube? constrictions.
    [Show full text]
  • Te2, Part Iii
    TERMINOLOGIA EMBRYOLOGICA Second Edition International Embryological Terminology FIPAT The Federative International Programme for Anatomical Terminology A programme of the International Federation of Associations of Anatomists (IFAA) TE2, PART III Contents Caput V: Organogenesis Chapter 5: Organogenesis (continued) Systema respiratorium Respiratory system Systema urinarium Urinary system Systemata genitalia Genital systems Coeloma Coelom Glandulae endocrinae Endocrine glands Systema cardiovasculare Cardiovascular system Systema lymphoideum Lymphoid system Bibliographic Reference Citation: FIPAT. Terminologia Embryologica. 2nd ed. FIPAT.library.dal.ca. Federative International Programme for Anatomical Terminology, February 2017 Published pending approval by the General Assembly at the next Congress of IFAA (2019) Creative Commons License: The publication of Terminologia Embryologica is under a Creative Commons Attribution-NoDerivatives 4.0 International (CC BY-ND 4.0) license The individual terms in this terminology are within the public domain. Statements about terms being part of this international standard terminology should use the above bibliographic reference to cite this terminology. The unaltered PDF files of this terminology may be freely copied and distributed by users. IFAA member societies are authorized to publish translations of this terminology. Authors of other works that might be considered derivative should write to the Chair of FIPAT for permission to publish a derivative work. Caput V: ORGANOGENESIS Chapter 5: ORGANOGENESIS
    [Show full text]
  • MDCT of Interatrial Septum
    Diagnostic and Interventional Imaging (2015) 96, 891—899 PICTORIAL REVIEW /Cardiovascular imaging MDCT of interatrial septum ∗ D. Yasunaga , M. Hamon Service de radiologie, pôle d’imagerie, CHU de Caen, avenue de la Côte-de-Nacre, 14033 Caen Cedex 9, France KEYWORDS Abstract ECG-gated cardiac multidetector row computed tomography (MDCT) allows precise Cardiac CT; analysis of the interatrial septum (IAS). This pictorial review provides a detailed description of Interatrial septum; the normal anatomy, variants and abnormalities of the IAS such as patent foramen ovale, con- Patent foramen genital abnormalities such as atrial septal defects as well as tumors and tumoral-like processes ovale; that develop on the IAS. Secundum ASD © 2015 Published by Elsevier Masson SAS on behalf of the Éditions françaises de radiologie. Introduction Major technical advances in computed tomography (CT) in recent years have made it pos- sible to use multidetector row CT (MDCT) in the field of cardiac imaging. Besides coronary arteries, ECG-gated cardiac MDCT provides high-resolution images of all cardiac structures. It is therefore important for radiologists to understand and be able to analyze the normal anatomical structures, variants and diseases of these different structures. This article provides an analysis of the interatrial septum (IAS) based on a pictorial review. After a short embryological and anatomical description, we will illustrate the nor- mal anatomy and variants of the IAS, anomalies such as patent foramen ovale (PFO), congenital diseases such as atrial septal defects (ASD) as well as tumors and tumoral-like processes that develop on the IAS. Abbreviations: ASA, atrial septal aneurysm; ASD, atrial septal defect; ECG, electrocardiogram; IAS, interatrial septum; IVC, inferior vena cava; IVS, interventricular septum; LV, left ventricle; M, myxoma; PFO, patent foramen ovale; RSPV, right superior pulmonary vein; RV, right ventricle; SVC, superior vena cava; MIP, maximal intensity projection; TEE, transesophageal echocardiography; TV, tricuspid valve.
    [Show full text]
  • Transcriptomic Analysis and Developmental Neural Transcript Identification in the Brittle Star Ophioplocus Esmarki
    Rochester Institute of Technology RIT Scholar Works Theses 4-27-2020 Transcriptomic Analysis and Developmental Neural Transcript Identification in the Brittle Star Ophioplocus esmarki Alexandria Shumway [email protected] Follow this and additional works at: https://scholarworks.rit.edu/theses Recommended Citation Shumway, Alexandria, "Transcriptomic Analysis and Developmental Neural Transcript Identification in the Brittle Star Ophioplocus esmarki" (2020). Thesis. Rochester Institute of Technology. Accessed from This Thesis is brought to you for free and open access by RIT Scholar Works. It has been accepted for inclusion in Theses by an authorized administrator of RIT Scholar Works. For more information, please contact [email protected]. 1 Transcriptomic Analysis and Developmental Neural Transcript Identification in the Brittle Star Ophioplocus esmarki By Alexandria Shumway A Thesis Submitted in Partial Fulfillment of the Requirements for the Degree of Master of Science in Bioinformatics Thomas H. Gosnell School of Life Sciences College of Science Rochester Institute of Technology Rochester, NY April 27, 2020 Rochester Institute of Technology Thomas H. Gosnell School of Life Sciences Bioinformatics Program 2 To: Head, Thomas H. Gosnell School of Life Sciences The undersigned state that Alexandria Juliana Shumway, a candidate for the Master of Science degree in Bioinformatics, has submitted her thesis and has satisfactorily defended it. This completes the requirements for the Master of Science degree in Bioinformatics at Rochester Institute of Technology. Name Date ____________________________ _______________________________ Dr. Hyla Sweet, Ph.D. Thesis Advisor ____________________________ _______________________________ Dr. Michael Osier, Ph.D. Committee Member ____________________________ _______________________________ Dr. Andre Hudson, Ph.D. Committee Member 3 1 ABSTRACT Ophioplocus esmarki is one species within a family of brittle stars that includes an abbreviated mode of development with a non-feeding, vitellaria larva.
    [Show full text]
  • Sox9 Is Required for Invagination of the Otic Placode in Mice ⁎ Francisco Barrionuevo A, , Angela Naumann B, Stefan Bagheri-Fam A,1, Volker Speth C, Makoto M
    Available online at www.sciencedirect.com Developmental Biology 317 (2008) 213–224 www.elsevier.com/developmentalbiology Sox9 is required for invagination of the otic placode in mice ⁎ Francisco Barrionuevo a, , Angela Naumann b, Stefan Bagheri-Fam a,1, Volker Speth c, Makoto M. Taketo d, Gerd Scherer a, Annette Neubüser b a Institute of Human Genetics and Anthropology, University of Freiburg, Breisacherstr. 33, D-79106 Freiburg, Germany b Developmental Biology, Institute of Biology 1, University of Freiburg, Hauptstrasse 1, D-79104 Freiburg, Germany c Cell Biology, Institute of Biology II, University of Freiburg, Schänzlestrasse 1, D-79104 Freiburg, Germany d Department of Pharmacology, Graduate School of Medicine, Kyoto University, Yoshida-Konoé-cho, Sakyo-ku, Kyoto 606-8501, Japan Received for publication 20 December 2007; revised 7 February 2008; accepted 8 February 2008 Available online 21 February 2008 Abstract The HMG-domain-containing transcription factor Sox9 is an important regulator of chondrogenesis, testis formation and development of several other organs. Sox9 is expressed in the otic placodes, the primordia of the inner ear, and studies in Xenopus have provided evidence that Sox9 is required for otic specification. Here we report novel and different functions of Sox9 during mouse inner ear development. We show that in mice with a Foxg1Cre-mediated conditional inactivation of Sox9 in the otic ectoderm, otic placodes form and express markers of otic specification. However, mutant placodes do not attach to the neural tube, fail to invaginate, and subsequently degenerate by apoptosis, resulting in a complete loss of otic structures. Transmission-electron microscopic analysis suggests that cell–cell contacts in the Sox9 mutant placodes are abnormal, although E-cadherin, N-cadherin, and beta-catenin protein expression are unchanged.
    [Show full text]
  • Cardiovascular System Heart Development Cardiovascular System Heart Development
    Cardiovascular System Heart Development Cardiovascular System Heart Development In human embryos, the heart begins to beat at approximately 22-23 days, with blood flow beginning in the 4th week. The heart is one of the earliest differentiating and functioning organs. • This emphasizes the critical nature of the heart in distributing blood through the vessels and the vital exchange of nutrients, oxygen, and wastes between the developing baby and the mother. • Therefore, the first system that completes its development in the embryo is called cardiovascular system. https://www.slideshare.net/DrSherifFahmy/intraembryonic-mesoderm-general-embryology Mesoderm is one of the three • Connective tissue primary germ layers that • Smooth and striated muscle • Cardiovascular System differentiates early in • Kidneys development that collectively • Spleen • Genital organs, ducts gives rise to all subsequent • Adrenal gland cortex tissues and organs. The cardiovascular system begins to develop in the third week of gestation. Blood islands develop in the newly formed mesoderm, and consist of (a) a central group of haemoblasts, the embryonic precursors of blood cells; (b) endothelial cells. Development of the heart and vascular system is often described together as the cardiovascular system. Development begins very early in mesoderm both within (embryonic) and outside (extra embryonic, vitelline, umblical and placental) the embryo. Vascular development occurs in many places. • Blood islands coalesce to form a vascular plexus. Preferential channels form arteries and veins. • Day 17 - Blood islands form first in the extra-embryonic mesoderm • Day 18 - Blood islands form next in the intra-embryonic mesoderm • Day 19 - Blood islands form in the cardiogenic mesoderm and coalesce to form a pair of endothelial heart tubes Development of a circulation • A circulation is established during the 4th week after the myocardium is differentiated.
    [Show full text]
  • Development of Right Ventricle
    DEVELOPMENT OF THE HEART II. David Lendvai M.D., Ph.D. Mark Kozsurek, M.D., Ph.D. • Septation of the common atrioventricular (AV) orifice. • Formation of the interatrial septum. • Formation of the muscular interventricular septum. • Appearance of the membranous interventricular septum and the spiral aorticopulmonary septum. right left septum primum septum primum septum primum septum primum septum primum septum primum foramen primum foramen primum septum primum septum primum foramen primum foramen primum septum primum septum primum foramen secundum foramen secundum foramen primum foramen primum septum primum foramen secundum septum primum foramen secundum foramen primum foramen primum septum primum septum primum foramen secundum foramen secundum septum secundum septum secundum foramen secundum foramen ovale foramen ovale septum primum septum primum septum secundum septum secundum foramen secundum foramen ovale foramen ovale septum primum septum primum septum secundum septum secundum foramen secundum septum primum foramen ovale foramen ovale septum primum SUMMARY • The septation of the common atrium starts with the appearance of the crescent-shaped septum primum. The opening of this septum, the foramen primum, becomes progressively smaller. • Before the foramen primum completly closes, postero-superiorly several small openings appear on the septum primum. These perforations coalesce later and form the foramen secundum. • On the right side of the septum primum a new septum, the septum secundum, starts to grow. The orifice of the septum secundum is the foramen ovale. • Finally two crescent-like, incomplete, partially overlapping septa exist with one hole on each. Septum secundum is more rigid and the septum primum on its left side acts as a valve letting the blood flow exclusively from the right to the left.
    [Show full text]
  • Echocardiographic Follow-Up of Patent Foramen Ovale and the Factors Affecting Spontaneous Closure
    Acta Cardiol Sin 2016;32:731-737 Brief Report doi: 10.6515/ACS20160205A Echocardiographic Follow-Up of Patent Foramen Ovale and the Factors Affecting Spontaneous Closure Ali Yildirim,1 Alperen Aydin,2 Tevfik Demir,1 Fatma Aydin,2 Birsen Ucar1 and Zubeyir Kilic1 Background: The aim of the present study was to evaluate the echocardiographic follow-up of patent foramen ovale, which is considered a potential etiological factor in various diseases, and to determine the factors affecting spontaneous closure. Methods: Between January 2000 and June 2012, records of 918 patients with patent foramen ovale were retrospectively reviewed. Patency of less than 3 mm around the fossa ovalis is called patent foramen ovale. Patients with cyanotic congenital heart diseases, severe heart valve disorders and severe hemodynamic left to right shunts were excluded from the study. The patients were divided into three groups based on age; 1 day-1 monthingroup1,1month-12monthsingroup2,andmorethan12monthsingroup3. Results: Of the 918 patients, 564 (61.4%) had spontaneous closure, 328 (35.8%) had patent foramen ovale continued, 15 (1.6%) patients had patent foramen ovale enlarged to 3-5 mm, 6 patients were enlarged to 5-8 mm, and in one patient patent foramen ovale reached to more than 8 mm size. Defect was spontaneously closed in 65.9% of the patients in group 1, 66.7% of the patients in group 2, and 52.3% of the patients in group 3. There was a negative correlation between the age of diagnosis and spontaneous closure (p < 0.05). Gender, prematurity and coexisting malformations such as patent ductus arteriosus and atrial septal aneurysm did not have any effect on spontaneous closure of patent foramen ovale (p > 0.05).
    [Show full text]
  • And Krox-20 and on Morphological Segmentation in the Hindbrain of Mouse Embryos
    The EMBO Journal vol.10 no.10 pp.2985-2995, 1991 Effects of retinoic acid excess on expression of Hox-2.9 and Krox-20 and on morphological segmentation in the hindbrain of mouse embryos G.M.Morriss-Kay, P.Murphy1,2, R.E.Hill1 and in embryos are unknown, but in human embryonal D.R.Davidson' carcinoma cells they include the nine genes of the Hox-2 cluster (Simeone et al., 1990). Department of Human Anatomy, South Parks Road, Oxford OXI 3QX The hindbrain and the neural crest cells derived from it and 'MRC Human Genetics Unit, Western General Hospital, Crewe are of particular interest in relation to the developmental Road, Edinburgh EH4 2XU, UK functions of RA because they are abnormal in rodent 2Present address: Istituto di Istologia ed Embriologia Generale, embryos exposed to a retinoid excess during or shortly before Universita di Roma 'la Sapienza', Via A.Scarpa 14, 00161 Roma, early neurulation stages of development (Morriss, 1972; Italy Morriss and Thorogood, 1978; Webster et al., 1986). Communicated by P.Chambon Human infants exposed to a retinoid excess in utero at early developmental stages likewise show abnormalities of the Mouse embryos were exposed to maternally administered brain and of structures to which cranial neural crest cells RA on day 8.0 or day 73/4 of development, i.e. at or just contribute (Lammer et al., 1985). Retinoid-induced before the differentiation of the cranial neural plate, and abnormalities of hindbrain morphology in rodent embryos before the start of segmentation. On day 9.0, the RA- include shortening of the preotic region in relation to other treated embryos had a shorter preotic hindbrain than the head structures, so that the otocyst lies level with the first controls and clear rhombomeric segmentation was pharyngeal arch instead of the second (Morriss, 1972; absent.
    [Show full text]
  • Development and Teratology of Cardiovascular and Lymphatic Systems
    Development and teratology of cardiovascular and lymphatic systems Repetition: Muscle tissue Beginning of the cardiovascular system development – the 3rd week: Hemangiogenesis (day 15 – 16) – blood islets (insulae sanguinae) in extraembryonic mesoderm and splanchnic mesenchyme of embryo Clusters of mesenchyme cells (angiogenic cells) differentiate into: - angioblasts endothelium (at the periphery of blood islets) - hemoblasts primitive erythrocytes (in the center of blood islets) Clusters of angiogenic cells form a "horseshoe-shaped" space between somatic and splanchnic layer of mesoderm = pericardial cavity. Two endothelial tubes arrise in splanchnic mesoderm. The ventral portion of these tubes forms the cardiogenic area with two heart tubes, while the lateral portions form the dorsal aortae. Germ disc: prosencephalon mesencephalon eye rhombencephalon heart lateral mesoderm somites small blood vessels blood islands 8,9 Spine primitive streak Initially, the cardiogenic area is located anterior to the prechordal plate and the neural plate. The growth of the central nervous system pulls the cardiogenic area and prechordal plate (buccopharyngeal membrane ventrally and caudally ( ). Cardiogenic region just cranial to the prechordal plate. The canalization of cardiogenic clusters in the splanchnic mesoderm results in the formation of the paired heart tubes. Folding of embryo and primitive gut separation from yolk sac. Fusion of the heart tubes a single heart tube is, temporarily attached to the dorsal side of the pericardial cavity by the
    [Show full text]
  • 6 Development of the Great Vessels and Conduction Tissue
    Development of the Great Vessels and Conduc6on Tissue Development of the heart fields • h:p://php.med.unsw.edu.au/embryology/ index.php?6tle=Advanced_-_Heart_Fields ! 2 Septa6on of the Bulbus Cordis Bulbus Cordis AV Canal Ventricle Looking at a sagital sec6on of the heart early in development the bulbus cordis is con6nuous with the ventricle which is con6nuous with the atria. As the AV canal shiOs to the right the bulbus move to the right as well. Septa6on of the Bulbus Cordis A P A P The next three slides make the point via cross sec6ons that the aorta and pulmonary arteries rotate around each other. This means the septum between them changes posi6on from superior to inferior as well. Septa6on of the Bulbus Cordis P A A P Septa6on of the Bulbus Cordis P A P A Migra6on of neural crest cells Neural crest cells migrate from the 3ed, 4th and 6th pharyngeal arches to form some of the popula6on of cells forming the aor6copulmonary septum. Septa6on of the Bulbus Cordis Truncal (Conal) Swellings Bulbus Cordis The cardiac jelly in the region of the truncus and conus adds the neural crest cells and expands as truncal swellings. Septa6on of the Bulbus Cordis Aorticopulmonary septum These swellings grow toward each other to meet and form the septum between the aorta and pulmonary artery. Aorta Pulmonary Artery Septa6on of the Bulbus Cordis Anterior 1 2 3 1 2 3 The aor6copulmonary septum then rotates as it moves inferiorly. However, the exact mechanism for that rota6on remains unclear. Septa6on of the Bulbus Cordis Aorta Pulmonary Artery Conal Ridges IV Foramen Membranous Muscular IV Endocarial Septum Interventricular Cushion Septum However, the aor6copulmonary septum must form properly for the IV septum to be completed.
    [Show full text]
  • The Functional Anatomy of the Heart. Development of the Heart, Anomalies
    The functional anatomy of the heart. Development of the heart, anomalies Anatomy and Clinical Anatomy Department Anastasia Bendelic Plan: Cardiovascular system – general information Heart – functional anatomy Development of the heart Abnormalities of the heart Examination in a living person Cardiovascular system Cardiovascular system (also known as vascular system, or circulatory system) consists of: 1. heart; 2. blood vessels (arteries, veins, capillaries); 3. lymphatic vessels. Blood vessels Arteries are blood vessels that carry blood away from the heart. Veins carry blood back towards the heart. Capillaries are tiny blood vessels, that connect arteries to veins. Lymphatic vessels: lymphatic capillaries; lymphatic vessels (superficial and deep lymph vessels); lymphatic trunks (jugular, subclavian, bronchomediastinal, lumbar, intestinal trunks); lymphatic ducts (thoracic duct and right lymphatic duct). Lymphatic vessels Microcirculation Microcirculatory bed comprises 7 components: 1. arterioles; 2. precapillaries or precapillary arterioles; 3. capillaries; 4. postcapillaries or postcapillary venules; 5. venules; 6. lymphatic capillaries; 7. interstitial component. Microcirculation The heart Heart is shaped as a pyramid with: an apex (directed downward, forward and to the left); a base (facing upward, backward and to the right). There are four surfaces of the heart: sternocostal (anterior) surface; diaphragmatic (inferior) surface; right pulmonary surface; left pulmonary surface. External surface of the heart The heart The heart has four chambers: right and left atria; right and left ventricles. Externally, the atria are demarcated from the ventricles by coronary sulcus (L. sulcus coronarius). The right and left ventricles are demarcated from each other by anterior and posterior interventricular sulci (L. sulci interventriculares anterior et posterior). Chambers of the heart The atria The atria are thin-walled chambers, that receive blood from the veins and pump it into the ventricles.
    [Show full text]