DOCSLIB.ORG

Interrogating the Development of Enteric Nervous System in Zebrafish Using Transcriptomics Sweta Roy-Carson Iowa State University

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
Interrogating the Development of Enteric Nervous System in Zebrafish Using Transcriptomics Sweta Roy-Carson Iowa State University Iowa State University Capstones, Theses and Graduate Theses and Dissertations Dissertations 2019 Interrogating the development of Enteric Nervous System in zebrafish using transcriptomics Sweta Roy-Carson Iowa State University Follow this and additional works at: https://lib.dr.iastate.edu/etd Part of the Bioinformatics Commons Recommended Citation Roy-Carson, Sweta, "Interrogating the development of Enteric Nervous System in zebrafish using transcriptomics" (2019). Graduate Theses and Dissertations. 17303. https://lib.dr.iastate.edu/etd/17303 This Dissertation is brought to you for free and open access by the Iowa State University Capstones, Theses and Dissertations at Iowa State University Digital Repository. It has been accepted for inclusion in Graduate Theses and Dissertations by an authorized administrator of Iowa State University Digital Repository. For more information, please contact [email protected]. Interrogating the development of Enteric Nervous System in zebrafish using transcriptomics by Sweta Roy-Carson A dissertation submitted to the graduate faculty in partial fulfillment of the requirements for the degree of DOCTOR OF PHILOSOPHY Major: Bioinformatics and Computational Biology Program of Study Committee: Drena Dobbs, Co-major Professor Matthew Hufford, Co-major Professor Carolyn Dill Donald Sakaguchi Heike Hofmann The student author, whose presentation of the scholarship herein was approved by the program of study committee, is solely responsible for the content of this dissertation. The Graduate College will ensure this dissertation is globally accessible and will not permit alterations after a degree is conferred. Iowa State University Ames, Iowa 2019 Copyright © Sweta Roy-Carson, 2019. All rights reserved. ii DEDICATION This thesis is dedicated to my grandfather Dr. Binoy Kumar Singh Roy for paving a way for this family to get education and follow their dreams. I know you wanted to see all of us succeed and reach the zenith of education dadu and you would have been very proud of your didi today! iii TABLE OF CONTENTS Page ACKNOWLEDGMENTS v ABSTRACT vii CHAPTER 1. INTRODUCTION 8 Enteric Nervous System 8 Subtypes of Enteric Neurons 17 Evolutionary conservation of ENS 22 Zebrafish as a Model Organism 24 Organization of the Thesis 25 References 26 Figures 37 Tables 39 CHAPTER 2. DEFINING THE TRANSCRIPTOMIC LANDSCAPE OF THE DEVELOPING ENTERIC NERVOUS SYSTEM AND ITS CELLULAR ENVIRONMENT 40 Abstract 40 Background 40 Materials and Methods 45 Results 49 Discussion 61 Conclusion 75 List of abbreviations 75 Ethics approval 75 Acknowledgement 76 References 76 Figures 90 Tables 99 iv CHAPTER 3. DISCOVERING DEVELOPMENTAL DYNAMICS OF ENTERIC NEURONS: ONE CELL AT A TIME 106 Abstract 106 Introduction 107 Materials and Methods 110 Results 115 Discussion 131 References 136 Figures 142 Tables 149 CHAPTER 4. GENERAL CONCLUSION 151 Introduction 151 Lineage-specific Transcription Profile of the Intestinal Cells 152 Subpopulation of Enteric Neurons Exist Throughout Development 154 Future Directions 156 Significance of the Dissertation 157 References 158 v ACKNOWLEDGMENTS I would like to start by thanking my guide and mentor, Dr. Julie Kuhlman who has taught me all about enteric nervous system. My major professor and the chair of my committee, Dr. Drena Dobbs, my co-major professor, Dr. Matthew Hufford, and my committee members, Dr. Carolyn Dill, Dr. Donald Sakaguchi and Dr. Heiki Hofmann, for their guidance and support throughout the course of this research. A special thanks to Dr. Hufford for his invaluable suggestions, advice and support in the past year. I would also like to extend a special thank you to Dr. Carolyn Dill, for providing me with a lab space and a ‘foster’ lab family. Apart from my committee I would also like to thank Dr. Stephan Schneider, who played an integral part in the initial phase of my PhD and Trish Stauble who has helped me in every step of the PhD journey starting even before I entered this country. I would like to thank my parents, Dr. Nikhil Kumar Roy and Mrs. Archana Roy, for their constant encouragement and support during not only my PhD but my whole life. They have made sacrifices that cannot be described in words. They have always put our needs and wants before their own and made sure that I achieved every goal in my life. My grandmother, Mrs. Lekha Roy, who has always shown me what it is to be a strong independent woman and been my go-to person for the times when I felt I had hit a dead-end. My little brother, Jyotirmoy Roy, was the one who showed me dreams and also had faith in me, that helped me move forward and trust myself. I want to thank my whole family who showed me the importance of education and filling my life with love, trust, learning and happiness which were such big ingredients in making me the person that I am today. I also want to thank my mother-in-law, Pamela Hundley, sister-in-law, Emily Carson and brother-in-law, Justin Stoll for being kind and caring and being my rock to fall back on in this country. vi I have been blessed with the best people as friends and I wanted to name each one of them because they played a very important part during my PhD. Ankita, Sabiha and Prerna, we started our masters together and we are still each other’s support. Vivek, Dharmin and Bhagyashree have been there to listen to and lessen my PhD life woes. We have shared laughter and tears together and I am grateful for you guys in my life. It’s hard to put into words how much you guys have helped me, especially Vivek who has shown me what resilience and patience means. You are an inspiration to so many and I thank the three of you for being my support and having faith in me. I want to thank Maitry for being my soul sister and listening to my silly complaints and making delicious food to always cheer me up. My lab family Kendra, Kevin and Natalia, who apart from listening to my everyday lab woes also helped me to move in the right direction. Jennifer Chang, Kannan Sankar and Gokul, who have been with me since my first year at the university and have literally taught me bioinformatics. And my friends who became my family, Divita, Nikhil, Pooja, Archit, Rahul and Amber. You have been my guide, my go-to people for the most miniscule to the most gigantic problems, my support and my inspirations. Thank you for being my people. A special shout out to Freya Roy (Rahul and Amber’s progeny), our goddaughter for being my little stress buster and filling my life with so much joy and happiness. Last but not the least I would like to give the biggest and most heartfelt thank you to my husband Joshua Carson. I wouldn’t have been able to graduate without your help. We have been through so much together especially because of the graduate school experience and we did it! You have motivated, encouraged, loved and trusted me. You have helped me solve all my problems, research or personal, and cleaning up all my messes. Thank you for helping me overcome my fears and having faith in me more than I did in myself. This degree is not just mine; it is ours. vii ABSTRACT The enteric nervous system (ENS) is the set of neurons that control the activity of the gastrointestinal system. These activities include secretion of digestive juices, absorption of food, and motility of the gut. The enteric neurons are derived from the neural crest cells (NCC) which migrate to the gut during development. We have a sparse knowledge of the genes and the signaling pathways that are known to be involved in the migration, specification, and differentiation of the enteric neurons from neural crest precursors. Malfunction in any of these processes hampers normal ENS development and can result in a variety of diseases including Hirschsprung’s disease, a disorder in which the distal intestinal tract lacks enteric neurons. With the aid of transcriptomic study, we aimed to understand the molecular basis behind the different processes of development of a functional enteric nervous system using zebrafish as our model organism. In my research, we were able to generate the transcriptome of the neuronal cells as well as of the microenvironment that is known to provide external signals to these neurons in a normal developing ENS. We were able to identify previously linked genes and pathways associated with ENS development and also ascertain a large number of novel candidate genes that might be potential regulators in driving a normal ENS development. We also tried to elucidate the heterogeneity that exists between enteric neurons by performing a single cell transcriptomic study. Our findings from this project provided an insight into the different genetic and molecular factors that are specific to the different developmental stages. Along with shedding a light on the developmental timeline, this project also assisted in unraveling the factors distinctive of the subpopulations of the enteric neurons that reside in the gastrointestinal tract. 8 CHAPTER 1. INTRODUCTION Enteric Nervous System The digestive system is responsible for nutrition absorption as well as removal of waste from our system. It is not so well-known that these processes are actually controlled by the complex network of neurons and glia, called the enteric nervous system (ENS), that reside in the gastrointestinal tract. The ENS, also known as the “second brain” in popular culture, forms the biggest part of the peripheral nervous system (PNS) and is capable of functioning without any input from the central nervous system (CNS). In mammals, the enteric neurons and glia are arranged into ganglia, and consists of phenotypically varied cells.
Load more

Recommended publications
  • Welcome to the New Open Access Neurosci
    Editorial Welcome to the New Open Access NeuroSci Lucilla Parnetti 1,* , Jonathon Reay 2, Giuseppina Martella 3 , Rosario Francesco Donato 4 , Maurizio Memo 5, Ruth Morona 6, Frank Schubert 7 and Ana Adan 8,9 1 Centro Disturbi della Memoria, Laboratorio di Neurochimica Clinica, Clinica Neurologica, Università di Perugia, 06132 Perugia, Italy 2 Department of Psychology, Teesside University, Victoria, Victoria Rd, Middlesbrough TS3 6DR, UK; [email protected] 3 Laboratory of Neurophysiology and Plasticity, Fondazione Santa Lucia, and University of Rome Tor Vergata, 00143 Rome, Italy; [email protected] 4 Department of Experimental Medicine, University of Perugia, 06132 Perugia, Italy; [email protected] 5 Department of Molecular and Translational Medicine, University of Brescia, 25123 Brescia, Italy; [email protected] 6 Department of Cell Biology, School of Biology, University Complutense of Madrid, Av. Jose Antonio Novais 12, 28040 Madrid, Spain; [email protected] 7 School of Biological Sciences, University of Portsmouth, Hampshire PO1 2DY, UK; [email protected] 8 Department of Clinical Psychology and Psychobiology, University of Barcelona, 08035 Barcelona, Spain; [email protected] 9 Institute of Neurosciences, University of Barcelona, 08035 Barcelona, Spain * Correspondence: [email protected] Received: 6 August 2020; Accepted: 17 August 2020; Published: 3 September 2020 Message from Editor-in-Chief: Prof. Dr. Lucilla Parnetti With sincere satisfaction and pride, I present to you the new journal, NeuroSci, for which I am pleased to serve as editor-in-chief. To date, the world of neurology has been rapidly advancing, NeuroSci is a cross-disciplinary, open-access journal that offers an opportunity for presentation of novel data in the field of neurology and covers a broad spectrum of areas including neuroanatomy, neurophysiology, neuropharmacology, clinical research and clinical trials, molecular and cellular neuroscience, neuropsychology, cognitive and behavioral neuroscience, and computational neuroscience.
    [Show full text]
  • The Creation of Neuroscience
    The Creation of Neuroscience The Society for Neuroscience and the Quest for Disciplinary Unity 1969-1995 Introduction rom the molecular biology of a single neuron to the breathtakingly complex circuitry of the entire human nervous system, our understanding of the brain and how it works has undergone radical F changes over the past century. These advances have brought us tantalizingly closer to genu- inely mechanistic and scientifically rigorous explanations of how the brain’s roughly 100 billion neurons, interacting through trillions of synaptic connections, function both as single units and as larger ensem- bles. The professional field of neuroscience, in keeping pace with these important scientific develop- ments, has dramatically reshaped the organization of biological sciences across the globe over the last 50 years. Much like physics during its dominant era in the 1950s and 1960s, neuroscience has become the leading scientific discipline with regard to funding, numbers of scientists, and numbers of trainees. Furthermore, neuroscience as fact, explanation, and myth has just as dramatically redrawn our cultural landscape and redefined how Western popular culture understands who we are as individuals. In the 1950s, especially in the United States, Freud and his successors stood at the center of all cultural expla- nations for psychological suffering. In the new millennium, we perceive such suffering as erupting no longer from a repressed unconscious but, instead, from a pathophysiology rooted in and caused by brain abnormalities and dysfunctions. Indeed, the normal as well as the pathological have become thoroughly neurobiological in the last several decades. In the process, entirely new vistas have opened up in fields ranging from neuroeconomics and neurophilosophy to consumer products, as exemplified by an entire line of soft drinks advertised as offering “neuro” benefits.
    [Show full text]
  • The Baseline Structure of the Enteric Nervous System and Its Role in Parkinson’S Disease
    life Review The Baseline Structure of the Enteric Nervous System and Its Role in Parkinson’s Disease Gianfranco Natale 1,2,* , Larisa Ryskalin 1 , Gabriele Morucci 1 , Gloria Lazzeri 1, Alessandro Frati 3,4 and Francesco Fornai 1,4 1 Department of Translational Research and New Technologies in Medicine and Surgery, University of Pisa, 56126 Pisa, Italy; [email protected] (L.R.); [email protected] (G.M.); [email protected] (G.L.); [email protected] (F.F.) 2 Museum of Human Anatomy “Filippo Civinini”, University of Pisa, 56126 Pisa, Italy 3 Neurosurgery Division, Human Neurosciences Department, Sapienza University of Rome, 00135 Rome, Italy; [email protected] 4 Istituto di Ricovero e Cura a Carattere Scientifico (I.R.C.C.S.) Neuromed, 86077 Pozzilli, Italy * Correspondence: [email protected] Abstract: The gastrointestinal (GI) tract is provided with a peculiar nervous network, known as the enteric nervous system (ENS), which is dedicated to the fine control of digestive functions. This forms a complex network, which includes several types of neurons, as well as glial cells. Despite extensive studies, a comprehensive classification of these neurons is still lacking. The complexity of ENS is magnified by a multiple control of the central nervous system, and bidirectional communication between various central nervous areas and the gut occurs. This lends substance to the complexity of the microbiota–gut–brain axis, which represents the network governing homeostasis through nervous, endocrine, immune, and metabolic pathways. The present manuscript is dedicated to Citation: Natale, G.; Ryskalin, L.; identifying various neuronal cytotypes belonging to ENS in baseline conditions.
    [Show full text]
  • Signalling Between Microvascular Endothelium and Cardiomyocytes Through Neuregulin Downloaded From
    Cardiovascular Research (2014) 102, 194–204 SPOTLIGHT REVIEW doi:10.1093/cvr/cvu021 Signalling between microvascular endothelium and cardiomyocytes through neuregulin Downloaded from Emily M. Parodi and Bernhard Kuhn* Harvard Medical School, Boston Children’s Hospital, 300 Longwood Avenue, Enders Building, Room 1212, Brookline, MA 02115, USA Received 21 October 2013; revised 23 December 2013; accepted 10 January 2014; online publish-ahead-of-print 29 January 2014 http://cardiovascres.oxfordjournals.org/ Heterocellular communication in the heart is an important mechanism for matching circulatory demands with cardiac structure and function, and neuregulins (Nrgs) play an important role in transducing this signal between the hearts’ vasculature and musculature. Here, we review the current knowledge regarding Nrgs, explaining their roles in transducing signals between the heart’s microvasculature and cardiomyocytes. We highlight intriguing areas being investigated for developing new, Nrg-mediated strategies to heal the heart in acquired and congenital heart diseases, and note avenues for future research. ----------------------------------------------------------------------------------------------------------------------------------------------------------- Keywords Neuregulin Heart Heterocellular communication ErbB -----------------------------------------------------------------------------------------------------------------------------------------------------------† † † This article is part of the Spotlight Issue on: Heterocellular signalling
    [Show full text]
  • The Epidermal Growth Factor Receptor Family As a Central Element for Cellular Signal Transduction and Diversification
    Endocrine-Related Cancer (2001) 8 11–31 The epidermal growth factor receptor family as a central element for cellular signal transduction and diversification N Prenzel, O M Fischer, S Streit, S Hart and A Ullrich Max-Planck Institut fu¨r Biochemie, Department of Molecular Biology, Am Klopferspitz 18A, 82152 Martinsried, Germany (Requests for offprints should be addressed to A Ullrich; Email: [email protected]) Abstract Homeostasis of multicellular organisms is critically dependent on the correct interpretation of the plethora of signals which cells are exposed to during their lifespan. Various soluble factors regulate the activation state of cellular receptors which are coupled to a complex signal transduction network that ultimately generates signals defining the required biological response. The epidermal growth factor receptor (EGFR) family of receptor tyrosine kinases represents both key regulators of normal cellular development as well as critical players in a variety of pathophysiological phenomena. The aim of this review is to give a broad overview of signal transduction networks that are controlled by the EGFR superfamily of receptors in health and disease and its application for target-selective therapeutic intervention. Since the EGFR and HER2 were recently identified as critical players in the transduction of signals by a variety of cell surface receptors, such as G-protein-coupled receptors and integrins, our special focus is the mechanisms and significance of the interconnectivity between heterologous signalling systems. Endocrine-Related Cancer (2001) 8 11–31 Introduction autophosphorylation of cytoplasmic tyrosine residues (reviewed in Ullrich & Schlessinger 1990, Heldin 1995, Cell surface receptors integrate a multitude of extracellular Alroy & Yarden 1997).
    [Show full text]
  • Head & Neck Surgery Course
    Head & Neck Surgery Course Parapharyngeal space: surgical anatomy Dr Pierfrancesco PELLICCIA Pr Benjamin LALLEMANT Service ORL et CMF CHU de Nîmes CH de Arles Introduction • Potential deep neck space • Shaped as an inverted pyramid • Base of the pyramid: skull base • Apex of the pyramid: greater cornu of the hyoid bone Introduction • 2 compartments – Prestyloid – Poststyloid Anatomy: boundaries • Superior: small portion of temporal bone • Inferior: junction of the posterior belly of the digastric and the hyoid bone Anatomy: boundaries Anatomy: boundaries • Posterior: deep fascia and paravertebral muscle • Anterior: pterygomandibular raphe and medial pterygoid muscle fascia Anatomy: boundaries • Medial: pharynx (pharyngobasilar fascia, pharyngeal wall, buccopharyngeal fascia) • Lateral: superficial layer of deep fascia • Medial pterygoid muscle fascia • Mandibular ramus • Retromandibular portion of the deep lobe of the parotid gland • Posterior belly of digastric muscle • 2 ligaments – Sphenomandibular ligament – Stylomandibular ligament Aponeurosis and ligaments Aponeurosis and ligaments • Stylopharyngeal aponeurosis: separates parapharyngeal spaces to two compartments: – Prestyloid – Poststyloid • Cloison sagittale: separates parapharyngeal and retropharyngeal space Aponeurosis and ligaments Stylopharyngeal aponeurosis Muscles stylohyoidien Stylopharyngeal , And styloglossus muscles Prestyloid compartment Contents: – Retromandibular portion of the deep lobe of the parotid gland – Minor or ectopic salivary gland – CN V branch to tensor
    [Show full text]
  • Glutamatergic Synaptic Plasticity in the Mesocorticolimbic System in Addiction
    REVIEW ARTICLE published: 20 January 2015 CELLULAR NEUROSCIENCE doi: 10.3389/fncel.2014.00466 Glutamatergic synaptic plasticity in the mesocorticolimbic system in addiction Aile N. van Huijstee and Huibert D. Mansvelder * Department of Integrative Neurophysiology, Center for Neurogenomics and Cognitive Research, Neuroscience Campus Amsterdam, VU University Amsterdam, Amsterdam, Netherlands Edited by: Addictive drugs remodel the brain’s reward circuitry, the mesocorticolimbic dopamine (DA) Arianna Maffei, SUNY Stony Brook, system, by inducing widespread adaptations of glutamatergic synapses. This drug-induced USA synaptic plasticity is thought to contribute to both the development and the persistence Reviewed by: Christian Luscher, Geneva of addiction. This review highlights the synaptic modifications that are induced by in vivo University Hospital, University of exposure to addictive drugs and describes how these drug-induced synaptic changes may Geneva, Switzerland contribute to the different components of addictive behavior, such as compulsive drug Fereshteh S. Nugent, Uniformed use despite negative consequences and relapse. Initially, exposure to an addictive drug Services University, USA induces synaptic changes in the ventral tegmental area (VTA). This drug-induced synaptic *Correspondence: Huibert D. Mansvelder, Department potentiation in the VTA subsequently triggers synaptic changes in downstream areas of of Integrative Neurophysiology, the mesocorticolimbic system, such as the nucleus accumbens (NAc) and the prefrontal Center
    [Show full text]
  • Oxytocin Effects in Mothers and Infants During Breastfeeding
    © 2013 SNL All rights reserved REVIEW Oxytocin effects in mothers and infants during breastfeeding Oxytocin integrates the function of several body systems and exerts many effects in mothers and infants during breastfeeding. This article explains the pathways of oxytocin release and reviews how oxytocin can affect behaviour due to its parallel release into the blood circulation and the brain. Oxytocin levels are higher in the infant than in the mother and these levels are affected by mode of birth. The importance of skin-to-skin contact and its association with breastfeeding and mother-infant bonding is discussed. Kerstin Uvnäs Moberg Oxytocin – a system activator increased function of inhibitory alpha-2 3 MD, PhD xytocin, a small peptide of just nine adrenoceptors . Professor of Physiology amino acids, is normally associated The regulation of the release of oxytocin Swedish University of Agriculture O with labour and the milk ejection reflex. is complex and can be affected by different [email protected] However, oxytocin is not only a hormone types of sensory inputs, by hormones such Danielle K. Prime but also a neurotransmitter and a as oestrogen and even by the oxytocin 1,2 molecule itself. This article will focus on PhD paracrine substance in the brain . During Breastfeeding Research Associate breastfeeding it is released into the brain of four major sensory input nervous Medela AG, Baar, Switzerland both mother and infant where it induces a pathways (FIGURES 2 and 3) activated by: great variety of functional responses. 1. Sucking of the mother’s nipple, in which Through three different release pathways the sensory nerves originate in the (FIGURE 1), oxytocin functions rather like a breast.
    [Show full text]
  • The Enteric Nervous System: a Second Brain
    The Enteric Nervous System: A Second Brain MICHAEL D. GERSHON Columbia University Once dismissed as a simple collection of relay ganglia, the enteric nervous system is now recognized as a complex, integrative brain in its own right. Although we still are unable to relate complex behaviors such as gut motility and secretion to the activity of individual neurons, work in that area is proceeding briskly--and will lead to rapid advances in the management of functional bowel disease. Dr. Gershon is Professor and Chair, Department of Anatomy and Cell Biology, Columbia University College of Physicians and Surgeons, New York. In addition to numerous scientific publications, he is the author of The Second Brain (Harper Collins, New York, 1998). Structurally and neurochemically, the enteric nervous system (ENS) is a brain unto itself. Within those yards of tubing lies a complex web of microcircuitry driven by more neurotransmitters and neuromodulators than can be found anywhere else in the peripheral nervous system. These allow the ENS to perform many of its tasks in the absence of central nervous system (CNS) control--a unique endowment that has permitted enteric neurobiologists to investigate nerve cell ontogeny and chemical mediation of reflex behavior in a laboratory setting. Recognition of the importance of this work as a basis for developing effective therapies for functional bowel disease, coupled with the recent, unexpected discovery of major enteric defects following the knockout of murine genes not previously known to affect the gut, has produced a groundswell of interest that has attracted some of the best investigators to the field. Add to this that the ENS provides the closest thing we have to a window on the brain, and one begins to understand why the bowel--the second brain--is finally receiving the attention it deserves.
    [Show full text]
  • Neurotransmitter Actions
    Central University of South Bihar Panchanpur, Gaya, India E-Learning Resources Department of Biotechnology NB: These materials are taken/borrowed/modified/compiled from various resources like research articles and freely available internet websites, and are meant to be used solely for the teaching purpose in a public university, and for serving the needs of specified educational programmes. Dr. Jawaid Ahsan Assistant Professor Department of Biotechnology Central University of South Bihar (CUSB) Course Code: MSBTN2003E04 Course Name: Neuroscience Neurotransmitter Actions • Excitatory Action: – A neurotransmitter that puts a neuron closer to an action potential (facilitation) or causes an action potential • Inhibitory Action: – A neurotransmitter that moves a neuron further away from an action potential • Response of neuron: – Responds according to the sum of all the neurotransmitters received at one time Neurotransmitters • Acetylcholine • Monoamines – modified amino acids • Amino acids • Neuropeptides- short chains of amino acids • Depression: – Caused by the imbalances of neurotransmitters • Many drugs imitate neurotransmitters – Ex: Prozac, zoloft, alcohol, drugs, tobacco Release of Neurotransmitters • When an action potential reaches the end of an axon, Ca+ channels in the neuron open • Causes Ca+ to rush in – Cause the synaptic vesicles to fuse with the cell membrane – Release the neurotransmitters into the synaptic cleft • After binding, neurotransmitters will either: – Be destroyed in the synaptic cleft OR – Taken back in to surrounding neurons (reuptake) Excitable cells: Definition: Refers to the ability of some cells to be electrically excited resulting in the generation of action potentials. Neurons, muscle cells (skeletal, cardiac, and smooth), and some endocrine cells (e.g., insulin- releasing pancreatic β cells) are excitable cells.
    [Show full text]
  • Regulation of Adipose Tissue Function and Metabolic Homeostasis
    REGULATION OF ADIPOSE TISSUE FUNCTION AND METABOLIC HOMEOSTASIS by Guoxiao Wang A dissertation submitted in partial fulfillment of the requirements for the degree of Doctor of Philosophy (Cellular and Molecular Biology) in the University of Michigan 2014 Doctoral committee: Associate Professor Jiandie D. Lin, Chair Associate Professor Peter Dempsey Professor Ormond MacDougald Professor Liangyou Rui Professor Alan R. Saltiel © Guoxiao Wang 2014 DEDICATION To my parents and my husband, for their unconditional love ii ACKNOWLEDGEMENTS I would like to give special thanks to my mentor Jiandie Lin, who inspires confidence, enhances criticism and drives me forward. He bears all the virtues of a good mentor, always available to students despite the tremendous demands on his time. By actively doing research himself, he led us from the front and served as a role model. He has created a lab that is scientifically intense yet nurturing. He celebrates everybody’s success and respects individual difference, allowing us to “smell the rose”. I also would like to thank Siming Li, senior research staff in our lab, who has provided tremendous help from the start of my rotation and throughout my thesis research. I want to thank all my labmates, for the help I receive and friendship I enjoy. Thank you Xuyun Zhao and Zhuoxian Meng for help on our collaborative projects. Thank you Zhimin Chen and Yuanyuan Xiao for sharing resources and ideas that moves my project forward. Thank you Zoharit Cozacov for being such a terrific technician. And thank you Qi Yu and Lin Wang for providing common reagents to allow the lab to run smoothly.
    [Show full text]
  • Internal State Dependent Odor Processing and Perception—The Role of Neuromodulation in the Fly Olfactory System
    REVIEW published: 30 January 2018 doi: 10.3389/fncel.2018.00011 Internal State Dependent Odor Processing and Perception—The Role of Neuromodulation in the Fly Olfactory System Sercan Sayin 1†, Ariane C. Boehm 1,2†, Johanna M. Kobler 1,2†, Jean-François De Backer 1 and Ilona C. Grunwald Kadow 1,2* 1 Neural Circuits and Metabolism, School of Life Sciences, Technische Universität München, Munich, Germany, 2 Chemosensory Coding, Max Planck Institute of Neurobiology, Martinsried, Germany Animals rely heavily on their sense of olfaction to perform various vital interactions with an ever-in-flux environment. The turbulent and combinatorial nature of air-borne odorant cues demands the employment of various coding strategies, which allow the animal to attune to its internal needs and past or present experiences. Furthermore, these internal needs can be dependent on internal states such as hunger, reproductive state and sickness. Neuromodulation is a key component providing flexibility under such conditions. Understanding the contributions of neuromodulation, such as sensory neuron sensitization and choice bias requires manipulation of neuronal activity on a local Edited by: and global scale. With Drosophila’s genetic toolset, these manipulations are feasible Christiane Linster, and even allow a detailed look on the functional role of classical neuromodulators Cornell University, United States such as dopamine, octopamine and neuropeptides. The past years unraveled various Reviewed by: mechanisms adapting chemosensory processing and perception to internal states such Thomas Dieter Riemensperger, Department of Molecular as hunger and reproductive state. However, future research should also investigate Neurobiology of Behaviour, Germany the mechanisms underlying other internal states including the modulatory influence Markus Rothermel, RWTH Aachen University, Germany of endogenous microbiota on Drosophila behavior.
    [Show full text]