Model Animals in Neuroendocrinology: From Worm to Mouse to Man
By Mike Ludwig
()
About this ebook
Model Animals in Neuroendocrinology: From Worm to Mouse to Man offers a masterclass on the opportunities that different model animals offer to the basic understanding of neuroendocrine functions and mechanisms of action and the implications of this understanding. The authors review recent advances in the field emanating from studies involving a variety of animal models, molecular genetics, imaging technologies, and behavior assays. These studies helped unravel mechanisms underlying the development and function of neuroendocrine systems. The book highlights how studies in a variety of model animals, including, invertebrates, fish, birds, rodents and mammals has contributed to our understanding of neuroendocrinology.
Model Animals in Neuroendocrinology provides students, scientists and practitioners with a contemporary account of what can be learnt about the functions of neuroendocrine systems from studies across animal taxonomy.
This is the seventh volume in the Masterclass in Neuroendocrinology Series, a co-publication between Wiley and the INF (International Neuroendocrine Federation) that aims to illustrate highest standards and encourage the use of the latest technologies in basic and clinical research and hopes to provide inspiration for further exploration into the exciting field of neuroendocrinology.
Read more from Mike Ludwig
Left Out I Wish They Were Little Again Rating: 0 out of 5 stars0 ratingsLeft Out of Green, Black or White Rating: 0 out of 5 stars0 ratingsMy Mom Is the Boss Rating: 0 out of 5 stars0 ratingsWednesday Rating: 0 out of 5 stars0 ratings
Related to Model Animals in Neuroendocrinology
Related ebooks
Animal Models and Human Reproduction Rating: 0 out of 5 stars0 ratingsMolecular Neuroendocrinology: From Genome to Physiology Rating: 0 out of 5 stars0 ratingsSomatic Genome Variation: in Animals, Plants, and Microorganisms Rating: 0 out of 5 stars0 ratingsHandbook of Innovations in Central Nervous System Regenerative Medicine Rating: 0 out of 5 stars0 ratingsNeurobiology of Motor Programme Selection: New Approaches to the Study of Behavioural Choice Rating: 0 out of 5 stars0 ratingsThe Membranes of Cells Rating: 0 out of 5 stars0 ratingsThe GnRH Neuron and its Control Rating: 0 out of 5 stars0 ratingsEssentials of Stem Cell Biology Rating: 3 out of 5 stars3/5The Wiley Handbook of Evolutionary Neuroscience Rating: 0 out of 5 stars0 ratingsGene Activity in Early Development Rating: 0 out of 5 stars0 ratingsPatterning and Cell Type Specification in the Developing CNS and PNS: Comprehensive Developmental Neuroscience Rating: 0 out of 5 stars0 ratingsGene Therapy in Neurological Disorders Rating: 0 out of 5 stars0 ratingsBasic Neurochemistry: Principles of Molecular, Cellular, and Medical Neurobiology Rating: 0 out of 5 stars0 ratingsThe Chlamydomonas Sourcebook: Volume 1: Introduction to Chlamydomonas and Its Laboratory Use Rating: 0 out of 5 stars0 ratingsGene Regulation, Epigenetics and Hormone Signaling Rating: 0 out of 5 stars0 ratingsFrontiers in Developmental Biology Rating: 0 out of 5 stars0 ratingsInsect Molecular Genetics: An Introduction to Principles and Applications Rating: 5 out of 5 stars5/5Insect Molecular Biology and Biochemistry Rating: 5 out of 5 stars5/5Neuroendocrinology of Stress Rating: 0 out of 5 stars0 ratingsBrain Lipids in Synaptic Function and Neurological Disease: Clues to Innovative Therapeutic Strategies for Brain Disorders Rating: 0 out of 5 stars0 ratingsThe Chlamydomonas Sourcebook: Volume 3: Cell Motility and Behavior Rating: 0 out of 5 stars0 ratingsRecent Trends In Livestock Innovative Technologies Rating: 0 out of 5 stars0 ratingsProtein Chaperones and Protection from Neurodegenerative Diseases Rating: 0 out of 5 stars0 ratingsStructure and Intrinsic Disorder in Enzymology Rating: 0 out of 5 stars0 ratingsSynaptic Transmission Rating: 0 out of 5 stars0 ratingsThe Neuroscience of Cocaine: Mechanisms and Treatment Rating: 2 out of 5 stars2/5Circadian Medicine Rating: 0 out of 5 stars0 ratingsFish Physiology: Fish Neuroendocrinology Rating: 0 out of 5 stars0 ratingsAdvances in Animal Experimentation and Modeling: Understanding Life Phenomena Rating: 0 out of 5 stars0 ratingsSerotonin: The Mediator that Spans Evolution Rating: 0 out of 5 stars0 ratings
Medical For You
Mating in Captivity: Unlocking Erotic Intelligence Rating: 4 out of 5 stars4/5The 40 Day Dopamine Fast Rating: 4 out of 5 stars4/5The Lost Book of Simple Herbal Remedies: Discover over 100 herbal Medicine for all kinds of Ailment Inspired By Barbara O'Neill Rating: 0 out of 5 stars0 ratingsMediterranean Diet Meal Prep Cookbook: Easy And Healthy Recipes You Can Meal Prep For The Week Rating: 5 out of 5 stars5/5Tight Hip Twisted Core: The Key To Unresolved Pain Rating: 4 out of 5 stars4/5Holistic Herbal: A Safe and Practical Guide to Making and Using Herbal Remedies Rating: 4 out of 5 stars4/5Adult ADHD: How to Succeed as a Hunter in a Farmer's World Rating: 4 out of 5 stars4/5The Vagina Bible: The Vulva and the Vagina: Separating the Myth from the Medicine Rating: 5 out of 5 stars5/5The Amazing Liver and Gallbladder Flush Rating: 5 out of 5 stars5/5Peptide Protocols: Volume One Rating: 4 out of 5 stars4/5Living Daily With Adult ADD or ADHD: 365 Tips o the Day Rating: 5 out of 5 stars5/5What Happened to You?: Conversations on Trauma, Resilience, and Healing Rating: 4 out of 5 stars4/5The Diabetes Code: Prevent and Reverse Type 2 Diabetes Naturally Rating: 4 out of 5 stars4/5ATOMIC HABITS:: How to Disagree With Your Brain so You Can Break Bad Habits and End Negative Thinking Rating: 5 out of 5 stars5/5Gut: The Inside Story of Our Body's Most Underrated Organ (Revised Edition) Rating: 4 out of 5 stars4/5The Hormone Reset Diet: Heal Your Metabolism to Lose Up to 15 Pounds in 21 Days Rating: 4 out of 5 stars4/5David D. Burns’ Feeling Good: The New Mood Therapy | Summary Rating: 4 out of 5 stars4/5Lifting the Fog: A specific guide to inattentive ADHD in adults Rating: 4 out of 5 stars4/5The Butchering Art: Joseph Lister's Quest to Transform the Grisly World of Victorian Medicine Rating: 4 out of 5 stars4/5The White Coat Investor: A Doctor's Guide to Personal Finance and Investing Rating: 4 out of 5 stars4/5The Song of the Cell: An Exploration of Medicine and the New Human Rating: 4 out of 5 stars4/5Herbal Healing for Women Rating: 4 out of 5 stars4/5Women With Attention Deficit Disorder: Embrace Your Differences and Transform Your Life Rating: 5 out of 5 stars5/5The Gene: An Intimate History Rating: 4 out of 5 stars4/5
Reviews for Model Animals in Neuroendocrinology
0 ratings0 reviews
Book preview
Model Animals in Neuroendocrinology - Mike Ludwig
Copyright
This edition first published 2019
© 2019 John Wiley & Sons Ltd
All rights reserved. No part of this publication may be reproduced, stored in a retrieval system, or transmitted, in any form or by any means, electronic, mechanical, photocopying, recording or otherwise, except as permitted by law. Advice on how to obtain permission to reuse material from this title is available at http://www.wiley.com/go/permissions.
The right of Mike Ludwig and Gil Levkowitz to be identified as the authors of the editorial material in this work has been asserted in accordance with law.
Registered Office(s)
John Wiley & Sons, Inc., 111 River Street, Hoboken, NJ 07030, USA
John Wiley & Sons Ltd, The Atrium, Southern Gate, Chichester, West Sussex, PO19 8SQ, UK
Editorial Office
The Atrium, Southern Gate, Chichester, West Sussex, PO19 8SQ, UK
For details of our global editorial offices, customer services, and more information about Wiley products visit us at www.wiley.com.
Wiley also publishes its books in a variety of electronic formats and by print-on-demand. Some content that appears in standard print versions of this book may not be available in other formats.
Limit of Liability/Disclaimer of Warranty
While the publisher and authors have used their best efforts in preparing this work, they make no representations or warranties with respect to the accuracy or completeness of the contents of this work and specifically disclaim all warranties, including without limitation any implied warranties of merchantability or fitness for a particular purpose. No warranty may be created or extended by sales representatives, written sales materials or promotional statements for this work. The fact that an organization, website, or product is referred to in this work as a citation and/or potential source of further information does not mean that the publisher and authors endorse the information or services the organization, website, or product may provide or recommendations it may make. This work is sold with the understanding that the publisher is not engaged in rendering professional services. The advice and strategies contained herein may not be suitable for your situation. You should consult with a specialist where appropriate. Further, readers should be aware that websites listed in this work may have changed or disappeared between when this work was written and when it is read. Neither the publisher nor authors shall be liable for any loss of profit or any other commercial damages, including but not limited to special, incidental, consequential, or other damages.
Library of Congress Cataloging-in-Publication Data
Names: Ludwig, Mike, editor. | Levkowitz, Gil, 1966- editor.
Title: Model animals in neuroendocrinology : from worm to mouse to man edited by Mike Ludwig, Gil Levkowitz.
Description: First edition. | Hoboken, NJ : Wiley, 2019. | Includes bibliographical references and index. | Identifiers: LCCN 2018008773 (print) | LCCN 2018009443 (ebook) | ISBN 9781119390886 (pdf) | ISBN 9781119390954 (epub) | ISBN 9781119390947 (cloth)
Subjects: | MESH: Neurosecretory Systems– physiology | Models, Animal | Genetic Phenomena | Veterinary Medicine
Classification: LCC QP356.4 (ebook) | LCC QP356.4 (print) | NLM WL 102 | DDC 612.8– dc23
LC record available at https://lccn.loc.gov/2018008773
Cover Design: Wiley
Cover image created by Nathalie Vladis;
White paper background © tomograf/Getty Images, Inc.
List of Contributors
Isabel Beets
Functional Genomics and Proteomics
Department of Biology
KU Leuven
Leuven
Belgium; and Cell Biology Division
MRC Laboratory of Molecular Biology
Cambridge
UK
Jakob Biran
Department of Poultry and Aquaculture
Agricultural Research Organization
Rishon Letziyon
Israel
Janna Blechman
Department of Molecular Cell Biology
Weizmann Institute of Science
Rehovot
Israel
Charline Borghgraef
Functional Genomics and Proteomics
Department of Biology
KU Leuven
Leuven
Belgium
Abderrahim Bouakkaz
Veterinary Institute
University Ibn Khaldoun
Tiaret
Algeria
Alamjeet K. Chauhan
Department of Biomedical and Molecular Sciences and Centre for Neuroscience Studies Queen's University
Kingston
Canada
Iain J. Clarke
Neuroscience Program
Monash Biomedical Discovery Institute
Department of Physiology
Monash University
Clayton
Australia
Juliette Cognié
PRC INRA U85 CNRS UMR7247 Université de Tours IFCE
Centre INRA Val de Loire
Nouzilly
France
Charlotte A. Cornil
Behavioral Neuroendocrinology lab
GIGA Neurosciences
University of Liège
Liège
Belgium
Roger D. Cox
MRC Harwell Institute
Mammalian Genetics Unit
Medical Research Council
Oxfordshire
UK
Scott F. Cummins
GeneCology Research Centre
University of the Sunshine Coast (USC)
Maroochydore
Queensland
Australia
Ludwig Czibere
Max Planck Institute of Psychiatry
Munich;
Labor Becker und Kollegen MVZ GbR
Munich
Germany
Shireen A. Davies
Institute of Molecular
Cell & Systems Biology
College of Medical
Veterinary & Life Sciences
University of Glasgow
Glasgow
UK
Caroline Decourt
PRC INRA U85 CNRS UMR7247 Université de Tours IFCE
Centre INRA Val de Loire
Nouzilly
France
Wouter De Haes
Functional Genomics and Proteomics
Department of Biology
KU Leuven
Leuven
Belgium; and Molecular and Functional Neurobiology
Department of Biology
KU Leuven
Leuven
Belgium
Flavie Derouin
PRC INRA U85 CNRS UMR7247 Université de Tours IFCE
Centre INRA Val de Loire
Nouzilly
France
Waljit S. Dhillo
Department of Investigative Medicine
Imperial College London
London
UK
Rebekka P. Diepold
Max Planck Institute of Psychiatry
Munich
Germany
Meghan Donovan
Department of Psychology and Program in Neuroscience
Florida State University
Tallahassee
USA
Julian A.T. Dow
Institute of Molecular
Cell & Systems Biology
College of Medical
Veterinary & Life Sciences
University of Glasgow
Glasgow
UK
Anne Duittoz
PRC INRA U85 CNRS UMR7247 Université de Tours IFCE
Centre INRA Val de Loire
Nouzilly
France
Rebecca Dumbell
MRC Harwell Institute
Mammalian Genetics Unit
Medical Research Council
Oxfordshire
UK
Francis J. P. Ebling
School of Life Sciences
Queen's Medical Centre
University of Nottingham
Nottingham
UK
Marina Eliava
Schaller Research Group on Neuropeptides
German Cancer Research Center
Heidelberg
Mario Engelmann
AG Neuroendokrinologie & Verhalten
Otto‐von‐Guericke‐Universität Magdeburg
Institut für Biochemie und Zellbiologie
Magdeburg
Germany; and Center for Behavioral Brain Sciences (CBBS)
Magdeburg
Germany
Auréline Forestier
PRC INRA U85 CNRS UMR7247 Université de Tours IFCE
Centre INRA Val de Loire
Nouzilly
France
Valery Grinevich
Schaller Research Group on Neuropeptides
German Cancer Research Center
Heidelberg; and
Central Institute of Mental Health
Mannheim
Germany
Rimma G. Gulevich
The Federal Research Center Institute of Cytology and Genetics
The Siberian Branch of the
Russian Academy of Sciences
Novosibirsk
Russia
Kenneth A. Halberg
Institute of Molecular,
Cell & Systems Biology
College of Medical,
Veterinary & Life Sciences
University of Glasgow
Glasgow
UK
Belinda A. Henry
Metabolic Disease and Obesity Program
Monash Biomedical Discovery Institute
Department of Physiology
Monash University
Clayton
Australia
Yury E. Herbeck
The Federal Research Center Institute of Cytology and Genetics
The Siberian Branch of the
Russian Academy of Sciences
Novosibirsk
Russia
Chioma Izzi‐Engbeaya
Department of Investigative Medicine
Imperial College London
London
UK
Rainer Landgraf
Max Planck Institute of Psychiatry
Munich
Germany
François Lecompte
CIRE platform
Centre INRA Val de Loire
Nouzilly
France
Gil Levkowitz
Department of Molecular Cell Biology
Weizmann Institute of Science
Rehovot
Israel
Jo E. Lewis
School of Life Sciences
Queen's Medical Centre
University of Nottingham
Nottingham
UK
Yan Liu
Department of Psychology and Program in Neuroscience
Florida State University
Tallahassee
USA
Samantha M. Logan
Institute of Biochemistry & Department of Biology
Carleton University
Ottawa
Canada
Neil S. Magoski
Department of Biomedical and Molecular Sciences and Centre for Neuroscience Studies
Queen's University
Kingston
Canada
Fabrice Reigner
UEPAO
Centre INRA Val de Loire
Nouzilly
France
Atsuko Saito
Department of Psychology
Sophia University
Tokyo
Japan
Liliane Schoofs
Functional Genomics and Proteomics
Department of Biology
KU Leuven
Leuven
Belgium
Darya V. Shepeleva
The Federal Research Center Institute of Cytology and Genetics
The Siberian Branch of the
Russian Academy of Sciences
Novosibirsk
Russia
Sergey V. Sotnikov
Max Planck Institute of Psychiatry
Munich
Germany; I. M. Sechenov First Moscow State Medical University
Moscow
Russia
Kenneth B. Storey
Institute of Biochemistry & Department of Biology
Carleton University
Ottawa
Canada
Raymond M. Sturgeon
Department of Biomedical and Molecular Sciences and Centre for Neuroscience Studies
Queen's University
Kingston
Canada
Selim Terhzaz
Institute of Molecular
Cell & Systems Biology
College of Medical
Veterinary & Life Sciences
University of Glasgow
Glasgow
UK
Lyudmila N. Trut
The Federal Research Center Institute of Cytology and Genetics
The Siberian Branch of the
Russian Academy of Sciences
Novosibirsk
Russia
Alexey E. Umriukhin
Max Planck Institute of Psychiatry
Munich
Germany
Sven Van Bael
Functional Genomics and Proteomics
Department of Biology
KU Leuven
Leuven
Belgium
Pieter Van de Walle
Molecular and Functional Neurobiology
Department of Biology
KU Leuven
Leuven
Belgium
Tomer Ventura
GeneCology Research Centre
University of the Sunshine Coast (USC)
Maroochydore
Queensland
Australia
Alex J. Watts
Institute of Biochemistry & Department of Biology
Carleton University
Ottawa
Canada
Zuoxin Wang
Department of Psychology and Program in Neuroscience
Florida State University
Tallahassee
USA
Einav Wircer
Department of Molecular Cell Biology
Weizmann Institute of Science
Rehovot
Israel
Lisa Yang
Department of Investigative Medicine
Imperial College London
London
UK
Dora Zelena
Department of Behavioural Neurobiology
Hungarian Academy of Sciences
Institute of Experimental Medicine
Budapest
Hungary;
Centre for Neuroscience
Szentágothai Research Centre
Institute of Physiology
Medical School
University of Pécs
Pécs
Hungary
Series Preface
This Series is a joint venture between the International Neuroendocrine Federation and Wiley Blackwell. The broad aim of the Series is to provide established researchers, trainees, and students with authoritative up‐to‐date accounts of the present state of knowledge, and prospects for the future across a range of topics in the burgeoning field of neuroendocrinology. The Series is aimed at a wide audience as neuroendocrinology integrates neuroscience and endocrinology. We define neuroendocrinology as the study of the control of endocrine function by the brain and the actions of hormones on the brain. It encompasses the study of normal and abnormal function, and the developmental origins of disease. It includes the study of the neural networks in the brain that regulate and form neuroendocrine systems. It also includes the study of behaviors and mental states that are influenced or regulated by hormones. It necessarily includes the understanding and study of peripheral physiological systems that are regulated by neuroendocrine mechanisms. Clearly, neuroendocrinology embraces many current issues of concern to human health and well‐being, but research on these issues necessitates reductionist animal models. Contemporary research in neuroendocrinology involves the use of a wide range of techniques and technologies, from subcellular to systems and whole‐organism level. A particular aim of the Series is to provide expert advice and discussion about experimental or study protocols in research in neuroendocrinology, and to further advance the field by giving information and advice about novel techniques, technologies, and interdisciplinary approaches. To achieve our aims each book is on a particular theme in neuroendocrinology, and for each book we have recruited an editor, or pair of editors, expert in the field, and they have engaged an international team of experts to contribute Chapters in their individual areas of expertise. Their mission was to give an up‐date of knowledge and recent discoveries, to discuss new approaches, ‘goldstandard’ protocols, translational possibilities, and future prospects. Authors were asked to write for a wide audience to minimize references, and to consider the use of video clips and explanatory text boxes; each Chapter is peer‐reviewed, and has a Glossary, and each book has a detailed index. We have been guided by an Advisory Editorial Board. Books published in the Series to date are:
Neurophysiology of Neuroendocrine Neurons (2014, eds W. E. Armstrong and J. G. Tasker)
Neuroendocrinology of Stress (2015, eds J. A. Russell and M. J. Shipston)
Molecular Neuroendocrinology: From Genome to Physiology (2016, eds D. Murphy and H. Gainer)
Computational Neuroendocrinology (2016, eds D. J. Macgregor and G. Leng)
Neuroendocrinology of Appetite (2016, eds, S. L. Dickson, J. G. Mercer)
The GnRH Neuron and its Control (2018, eds, A. E. Herbison , T. M. Plant)
Feedback and suggestions are welcome.
John A. Russell, University of Edinburgh,
and William E. Armstrong, University of Tennessee
Advisory Editorial Board:
Ferenc A. Antoni, Egis Pharmaceuticals PLC, Budapest
Tracy Bale, University of Pennsylvania
Rainer Landgraf, Max Planck Institute of Psychiatry, Munich
Gareth Leng, University of Edinburgh
Stafford Lightman, University of Bristol
Andrew Loudon, University of Manchester
International Neuroendocrine Federation – www.isneuro.org
Preface
Neuroendocrinology is about things that matter for the survival of the species. Neuroendocrine systems govern all aspects of reproduction: puberty, the ovarian cycle, mating, bonding, aggression, pregnancy, parturition, lactation and how maternal behavior is controlled. They guide how we respond to stress, injury and infection, our appetites for food and water, how we use the energy that we take in, and the daily rhythms of our bodies. They give us a stable blood pressure, blood volume, electrolyte balance, and body temperature. Neuroendocrine processes underpin fundamental physiological, molecular biological and genetic principles such as the regulation of gene transcription and translation, the mechanisms of chemical neurotransmission and intracellular and systemic feedback control systems. Neuroendocrine dysfunction due to genetic or other deficits can lead, for example, to infertility, impotence, precocious or delayed puberty, defective or excessive growth, obesity and anorexia, Cushing's Syndrome, hypertension or thyroid disorders and many neurological and behavior disorders.
The foundations of modern neuroendocrinology date to the early 20th century, when the pioneering work of Berta and Ernst Sharrer established the concept of neurosecretion using both invertebrate and vertebrate animal models. During research for his PhD, Ernst Scharrer used the European minnow (Phoxinus laevis) to describe some hypothalamic neurons that contained secretory droplets (so‐called nerve‐gland cells
) – and hypothesized that these could be secreted in a fashion similar to that in exocrine glands. This observation challenged the dogma that neural tissue was exclusively involved in electrical transmission. In parallel studies, his wife Berta, using mainly insects (cockroach), reinforced the concept of neurosecretion, suggesting that this was a common phenomenon found in diverse species, and which therefore, might be a general physiological event [1, 2].
Many findings in neuroendocrinology have been extrapolated from animal models to humans based on phylogeny‐ and morphology‐based studies. Comparative studies have revealed the existence of similar distribution patterns of peptide‐containing neurones within homologous hypothalamic nuclei of evolutionary distant species. The sequences and structure of hypothalamic peptides and releasing hormones have been remarkably preserved throughout the evolutionary tree, and even exhibit similar biological functions, including complex behavioral effects. This is clearly exemplified by the nonapeptides vasopressin and oxytocin and their non‐mammalian homologs. Both peptides are synthesised by homologous groups of hypothalamic neurones, and, when released centrally, are involved in social behaviors in several classes of animals, such as fish, amphibians, and mammals (including humans). Notably, the essential neuronal nature of neuroendocrine neurons, electrical excitability and synaptic connectivity, was first established in 1964 by Eric Kandel in a lower vertebrate, the goldfish [3] before its confirmation in mammals.
Nowadays, the advent of translational medicine to find new strategies and therapeutic interventions for current major diseases (e.g. depression and obesity), has raised the importance of elucidating the normal and pathological mechanisms and pathways underpinning these diseases. Recent technologies for producing transgenic mice and rats carrying additional genetic material, and knockout animals in which genetic material is deleted, resulted in developments such as tissue‐specific methods of knocking out genes (Cre‐Lox system), methods of turning on or off gene transcription in vivo (using tetracycline‐ or tamoxifen), and methods for identifying (via fluorescent proteins) or removing entire cell groups (diphtheria‐toxin receptor‐knockin). Transgenic technologies are also powerful in other species. For example, the fruit fly (Drosophila melanogaster), the nematode worm (Caenorhabditis elegans) and the zebra fish (Danio rerio) are species that are amenable to genetic manipulation and analysis, so that many different mutants and detailed genetic maps are readily available. The current advances in targeted genomic editing (CrispR), together with the use of state‐of‐art techniques, such as optogenetics and pharmacogenetics, allow us to scrutinise neuroendocrine systems in‐depth, unleashing the potential to unravel complex interactions among neural, hormonal, and peripheral systems that underlie physiological functions in health and disease.
The list of model animals is long, but this book covers necessarily only a limited range of model animals, including invertebrates, fish, birds, rodents and large mammals to explain the opportunities that each model animal gives to our basic understanding of neuroendocrine functions and mechanisms of action and the translational implications of this understanding. Some of these model animals are well established and widely used to address numerous questions, some are selected for the study of specific physiological processes and behaviors (e.g. squirrels for hibernation, voles for pair bonding, dogs for domestication).
The main objective of this volume is to demonstrate the value of different model animals, and their growing importance for neuroendocrine research. We aimed to write this book in such a way as to provide an overview of sufficient depth for a new scientist in the field to understand the diverse opportunities that different model animals provide for neuroendocrine research. We hope that this book will also appeal to senior scientists who are planning to shift their studies to a different model organism, or to embrace an additional model, and those in related disciplines who require a contemporary account of the field and the methodological approaches used. This volume aims to encourage interdisciplinary approaches and is expected to appeal to an audience with a basic, clinical or therapeutic interest in research into neuroendocrinology.
Mike Ludwig
Gil Levkowitz
References
1 Scharrer, E. (1928). Die Lichtempfindlichkeit Blinder Elritzen. Untersuchungen Über das Zwischenhirn der Fische I. J Comp Physiol A; 7(1): 1–38.
2 Scharrer, E. and B. Scharrer (1945). Neurosecretion. Physiol Rev 25(1): 171–181.
3 Kandel, E.R. (1964). Electrical properties of hypothalamic neuroendocrine cells J Gen Physiol. 47: 691–717.
Acknowledgments
The editors of this book would like to thank Dr David Apps for extensive expert editorial attention to issues of style, syntax and grammar throughout all chapters and to Nathalie Vladis for drawing the cover art.
About the Companion Website
Don't forget to visit the companion website for this book:
www.wiley.com/go/ludwig/modelanimals c03f001
There you will find valuable material designed to enhance your learning, including:
Videos
Figures
Scan this QR code to visit the companion website
flastg001Chapter 1
Neuroendocrine Regulation in the Genetic Model C. elegans
Charline Borghgraef¹*, Pieter Van de Walle²*, Sven Van Bael¹, Liliane Schoofs¹, Wouter De Haes¹,²§ and Isabel Beets¹,³§
¹Functional Genomics and Proteomics, Department of Biology, KU Leuven, Leuven, Belgium
²Molecular and Functional Neurobiology, Department of Biology, KU Leuven, Leuven, Belgium
³Cell Biology Division, MRC Laboratory of Molecular Biology, Cambridge, UK
1.1 A brief history on the model organism C. elegans
Research on the neurobiology of Caenorhabditis elegans has its roots in the 1960s, when Sydney Brenner proposed to use the nematode as a model organism for studying development and functioning of the nervous system. Brenner (Nobel Prize 2002) pioneered C. elegans genetics, by isolating and genetically mapping hundreds of mutant strains. Two decades later, John White and colleagues reconstructed the anatomy and synaptic connections (connectome) of all 302 C. elegans neurons in the adult hermaphrodite from electron micrographs. More recently, the wiring diagram of the posterior mating circuit in the adult male was mapped. Because C. elegans has a fixed number of somatic cells, researchers were able to construct a complete cell lineage by tracking the fate of each cell from fertilization to adulthood. This work was achieved by John Sulston and Robert Horvitz (Nobel Prize 2002), Judith Kimble, David Hirsh and Einhard Schierenberg. The neuronal connectome and cell lineage map allowed unprecedented insight into the worm's anatomy, development and neuronal makeup. These resources provided the basis for several key discoveries, including the characterization of genes regulating programmed cell death and axon guidance.
At the start of the genomic era in the 1990s, C. elegans was one of the simplest and best‐studied animals available for undertaking whole‐genome sequencing. The nematode was the first multicellular eukaryote to have its genome sequenced, a project completed in 1998. In the same year, RNA‐interference (RNAi) was first demonstrated by Andrew Fire and Craig Mello (Nobel Prize 2006) using C. elegans. It has since been widely adopted as a tool for gene silencing in many organisms. C. elegans' transparent body facilitated another breakthrough that revolutionized the analysis of gene function. In 1994, Martin Chalfie (Nobel Prize 2008) showed that DNA encoding green fluorescent protein (GFP) could be used to mark gene expression in vivo in C. elegans. These landmark discoveries have been fundamental for establishing C. elegans as a versatile, genetic model system which is used today for studying questions on diverse research topics ranging from aging to metabolism, behavior, innate immunity and neuroendocrinology.
1.2 C. elegans genetics and anatomy
C. elegans is a small, free‐living nematode that has two sexual forms: hermaphrodites and males (Figure 1.1). Both sexes have five autosomal chromosomes. Males have one X chromosome resulting from a spontaneous non‐disjunction during meiosis, which occurs at low frequency (0.1%). After mating, the proportion of male progeny rises to 50%. Self‐fertilizing hermaphrodites have two X chromosomes. They are easily cultivated and ensure transfer of homozygous mutations to the next generation. Therefore, they are studied far more commonly than males and used to maintain strain collections. C. elegans strains can be stored long‐term by freezing them in a glycerol‐rich solution at −80°C or in liquid nitrogen. The C. elegans research community has generated an extensive resource of mutants for most genes, which are summarized in the online database ‘Wormbase’, together with manually curated functional descriptions of all genes (www.wormbase.org). Over 21,000 protein‐coding genes are annotated in the C. elegans genome (∼100 Mb), over 30% of which have human orthologs.
c01f001Figure 1.1 Schematic body plans of adult C. elegans hermaphrodite and male, showing the pharynx in orange, intestine in yellow, gonads in green and cuticle in grey. In hermaphrodites, the gonads are connected to the spermatheca (dark green), followed by the uterus with eggs (blue). Males have a single gonad, which is connected to the vas deferens (dark green) and male‐specific copulatory apparatus (blue), consisting of a fanned tail with copulatory spicules.
Adult C. elegans have an invariant number of somatic cells (eutely). Adult hermaphrodites measure around 1 mm in length and consist of 959 somatic nuclei, including 302 neurons. The adult male comprises 1031 somatic nuclei with 381 neurons. Most male‐specific neurons are located in the copulatory circuits of the male tail. Similar to other nematodes, C. elegans has a simple body plan (Figure 1.1) that consists of an unsegmented inner and outer tube, separated by the pseudocoelomic body cavity. The outer tube contains the cuticle, the hypodermis, the muscles, the neurons and the excretory system; the inner tube comprises the pharynx, the intestine and the gonads. The most important endocrine sites in C. elegans are the nervous system, the intestinal and the gonadal tissues.
The small nervous system of C. elegans and its fully mapped connectome make it a prime model for studying the neuroendocrine control of physiology and behavior. The C. elegans neural network consists of two distinct systems: the large somatic nervous system (282 neurons) and a smaller pharyngeal nervous system (20 neurons) (Figure 1.2). The pharyngeal nervous system drives pumping of the pharynx and operates largely autonomously. The majority of neurons in the somatic nervous system have cell bodies in the head. Their processes are organized in a nerve ring surrounding the pharynx. A smaller number of somatic neurons are located in the lateral and tail ganglia, with processes that often project into the nerve ring. Sensory perception primarily relies on two symmetrically placed multicellular sensory organs, called amphids, which are located in the head. They can detect a wide range of sensory cues including olfactory, mechanical and water‐soluble chemical stimuli. Smaller sensory organs, termed phasmids, are laterally located in the tail and are involved in the integration of stimuli sensed at the anterior and posterior parts of the body. For example, the phasmid neurons PHA and PHB, together with the polymodal amphid neuron ASH, mediate behavioral responses to chemical repellants.
c01f002Figure 1.2 Schematic wiring diagram of the C. elegans hermaphrodite nervous system, which includes 20 pharyngeal neurons (blue) and 282 neurons of the somatic nervous system. Cell bodies of neurons in the somatic nervous system are primarily located in ganglia in the head and tail, and along the ventral nerve cord (VNC). Most head neurons are organized around a ring‐shaped bundle of neuron processes, called the nerve ring. Over 60% of all somatic neurons project axons or processes into the nerve ring. The detection of sensory stimuli relies largely on the amphid neurons (green) in the head and phasmid neurons (red) in the tail.
The worm's alimentary system – comprising the pharynx, intestine and anus – is involved in feeding and digestion. Since C. elegans consumes microorganisms, the intestine is also involved in immune and stress responses. In addition, the intestine and pharynx play important roles in the regulation of metabolic and endocrine processes, and in the storage of macromolecules. For example, the intestine is a main target site for insulin‐like peptides. The somatic gonad also expresses several bioactive peptides and is thought to be the main site of synthesis of steroid hormones, termed dafachronic acids, which are involved in the regulation of development and lifespan. Males have only one gonadal arm for spermatogenesis (Figure 1.1). Hermaphrodites have two gonadal arms (Figure 1.1), in which oogenesis occurs in the distal tips. Hermaphrodite spermatogenesis takes place during development in the distal gonad, and sperm is stored in the spermatheca near the uterus.
1.3 C. elegans life‐history
C. elegans is found worldwide, predominantly in humid and temperate environments. The nematode is commonly present in composting plant material, on plant stems, in rotting fruit and other bacteria‐rich substrates. Its life‐cycle consists of an embryonic stage, four larval stages (L1 to L4) and an adult stage. The timing of transitions between each stage depends on ambient temperature, but usually takes between three to four days from egg to adulthood (Figure 1.3). One of C. elegans' appealing features is its short generation time. The embryogenesis of hermaphrodites mainly occurs ex utero and lasts ∼11 hours (at 20°C). The transition through the four larval stages typically requires ∼65 hours. The end of each larval stage is characterized by a phase of lethargy and molting of the cuticle. In hermaphrodites, spermatogenesis takes place only during the fourth larval stage, after which oocytes are exclusively produced. Adults can lay eggs for up to 5 or 6 days and live for up to 3 weeks. C. elegans is easy to cultivate in the laboratory as the only requirements are nematode growth medium (NGM) agar plates seeded with Escherichia coli OP50 bacteria and a temperature‐controlled incubator. Worms are typically grown at 20°C. Under these conditions, animals should be transferred to fresh plates every two to three days.
c01f003Figure 1.3 Lifecycle of C. elegans at 20°C. Adult hermaphrodites can lay eggs after self‐fertilization or mating with a male. After 11‐16 hours, the eggs hatch and develop into L1 larvae. These larvae can enter a reversible developmental arrest if starved. L1 develop subsequently into L2, L3, and L4 larvae, or go into another arrested developmental state termed ‘dauer’ during the first larval molt, when food is scarce, conditions are stressful, or the environment is crowded. Stress‐resistant dauer larvae can rejoin the normal developmental cycle by molting into L4 larvae when conditions improve. L4 larvae molt once more into fertile adults. The entire development, from egg to adult, takes around 3 days.
During larval development, several checkpoints exist that may cause C. elegans to enter states of arrested development and increased stress resistance. Transfer into these arrested states is primarily controlled by the amphids and relies on neuroendocrine cascades, including insulin‐like and transforming growth factor (TGF)‐β‐like signaling. If worms hatch in an environment that lacks food, they enter a state of altered metabolism, termed L1 diapause, in which they can survive for up to two weeks. L1 arrested worms resume their reproductive development when food is present. A second state of arrested development is an alternative third larval stage, termed the ‘dauer stage’, which can be induced by crowding, the lack of food, or the presence of other stressors in the environment (Figure 1.3). Dauer larvae are more resistant to stress and can live over four times longer than C. elegans adults. When conditions become favorable, the dauer larva resumes its molt into the L4 and adult stages. The dauer state is referred to as a ‘non‐aging state’, as it does not affect the lifespan of C. elegans at the adult stage.
The lifespan of adult C. elegans is two to three weeks. Upon aging, adults display several morphological defects, some of which are reminiscent of human ageing. For example, muscle mass is lost and the cuticle becomes increasingly disorganized, leading to the formation of ‘wrinkles’ and loss of cuticular stability. Aging worms also shrink in size and show gradual decline in their ability to learn and retrieve memory. C. elegans is a prime model for the genetic study of aging, including cognitive decline which is regulated by insulin‐like endocrine signaling.
1.4 Neuroendocrine signaling systems in C. elegans
1.4.1 Neuropeptides
C. elegans has a broad repertoire of neuropeptides that are typically derived from inactive precursor proteins, containing one or multiple neuropeptides. The C. elegans genome encodes four genes for proprotein convertases (PCs) that cleave peptides from their precursor (kpc‐1, egl‐3, aex‐5 and bli‐4), all of which display homology to the Kex2/Subtilisin family of PCs in humans. After proteolysis, carboxypeptidases, which in C. elegans are encoded by egl‐21, cpd‐1, and cpd‐2 genes, catalyze the removal of paired basic amino acids at the cleavage site. Many neuropeptides require post‐translational modifications that are essential for their biological activity and stability in vivo. These include C‐terminal amidation, N‐terminal conversion of glutamate to pyroglutamate, glycosylation, acetylation, sulfation and phosphorylation.
The C. elegans genome encodes at least 154 neuropeptide precursor genes that are classified in three families: the insulin‐like (INS) peptides, the RFamide (FLP) peptides, and all other neuropeptide‐like (NLP) proteins. The majority of neuropeptides, with the exception of the insulin‐like peptides, are thought to signal via G protein‐coupled receptors (GPCRs), of which more than 150 genes are predicted in the C. elegans