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The Coiled Spring H O W L I F E B E G I N S The Coiled Spring H O W L I F E B E G I N S Ethan Bier University of California, San Diego La Jolla, California C S H L P OLD PRING ARBOR ABORATORY RESS Cold Spring Harbor, New York The Coiled Spring: How Life Begins © 2000 by Cold Spring Harbor Laboratory Press All rights reserved Printed in the United States of America Acquisition/Developmental EditorJudy Cuddihy Project CoordinatorInez Sialiano Production EditorPat Barker Interior DesignerDenise Weiss Cover DesignerEd Atkeson/Berg Design Front Cover Art:Painting by Judy Cuddihy Library of Congress Cataloging-in-Publication Data Bier, Ethan. The coiled spring : how life begins / Ethan Bier. p. cm. Includes bibliographical references and index. ISBN 0-87969-563-3 (pbk. : alk. paper)—ISBN 0-87969-562-5 (cloth: alk. paper) 1. Developmental genetics. I. Title. 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For a complete catalog of Cold Spring Harbor Laboratory Press publications, visit our World Wide Web Site http://www.cshl.org This book is dedicated to my parents and my son Benjamin Contents Preface, xi Foreword, xiii Introduction, 1 1 The Central Dogma of Biology, 7 The “central dogma”—that DNA, the heritable genetic material, is copied into RNA, which directs the synthesis of protein—is a basic tenet of life. How this idea guided important discoveries in developmental biology is described using examples of the Gurdon experiment, which proved that all cells in a frog contain the same genetic information; the nature of heritable mutations; and the Mangold–Spemann experiment, which showed that a specialized region of the frog embryo directs the formation of the nervous system. 2 Molecular Methods for Analyzing Development, 35 Techniques developed during the past 30 years have provided pow- erful tools for analyzing development. The most important of these—gene cloning, methods for showing gene activity in developing embryos, and methods for analyzing and manipulating gene activity—are described. 3 Establishing the Primary Axes of Fruit Fly Embryos, 49 Establishing a plan or pattern for development of the fertilized egg is the key event in producing a differentiated embryo with different tissue types. This process in the fruit fly is described using the ground-breaking work of Eric Wieschaus, Christiane Nüsslein- Volhard, Gerd Jürgens, and Ed Lewis, who found the genes that are required for normal development by looking for mutants in which development was abnormal. (cid:2) vii(cid:2) viii (cid:2) Contents 4 Patterning Fly Appendages and Eyes, 87 Assembly of the adult fruit fly during metamorphosis is the focus here, particularly the development of fly wings, legs, and eyes. These processes are explained by describing the small set of genes that define the primary axes of the wing, linking the formation of an adult structure to earlier events in embryonic development, and discussing the question of whether or not there are “master” genes that direct the formation of eyes. 5 Establishing the Primary Axes of Vertebrate Embryos, 113 Although higher on the evolutionary scale than flies, vertebrate embryos use many of the same genes as the fly embryo to set up the primary body axes and tissue types. Even more remarkable is the fact that vertebrate genes involved in early embryonic development can replace their fruit fly counterparts in developing flies and vice versa. The experiments that revealed these astonishing facts and their implications are discussed. 6 Patterning Vertebrate Appendages and Eyes, 135 Here again is the unexpected finding that genes involved in defin- ing adult structures such as appendages and eyes are the same in vertebrates and flies. The evolutionary implications of the similarities of fly and vertebrate development are discussed, and the most recent common ancestor of flies and vertebrates is reconstructed. 7 Establishing the Primary Axes of Plant Embryos, 159 Using the mustard plant embryo as an example, important differ- ences between plant and animal development are illustrated. The polarization of the plant embryo along the shoot-to-root axis, as well as radial organization, is shown using analysis of mutant plants that generate abnormal embryos. Similarities between plant and animal development are also discussed. 8 Patterning Plant Appendages, 177 The formation of the plant equivalent of appendages—flowers, fruits, and leaves—is described. Topics include how flower buds develop into four basic organ types, Goethe’s inference that all or- gans of the flower are modified forms of leaves (he was right!), and the finding that although very different genes in plants and animals control formation of flat structures such as leaves or wings, these genes work by surprisingly similar mechanisms. 9 The Future of Biology and Man, 199 We are very rapidly making progress in understanding how genes control development and other human characteristics. The social Contents (cid:2) ix implications of these discoveries—how we think of ourselves as humans and how these discoveries can change our nature—are con- sidered using topics such as the Human Genome Project, which is determining the complete genetic blueprint of humans; the implications of our newfound knowledge of the genetics of human dis- ease and health; and genetic engineering of plants and animals. How the world of science fiction views these topics is also consid- ered. Color Plate Section, following page 112 Glossary, 217 References and Additional Reading, 233 Credits, 241 Index, 245 Bioboxes Landmark progress in science is made by pioneering individuals. Those responsible for some of the key discoveries in developmental biology are highlighted in “Bioboxes” that appear throughout the text. These scientists represent the human side of the wonder- ful discoveries described in this book. John Gurdon p. 10 Hilde Mangold p. 32 Johann Wolfgang von Goethe p. 44 Christiane Nüsslein-Volhard p. 61 Eric Wieschaus p. 62 Ed Lewis p. 66 Mike Levine p. 83 Sean Carroll p. 91 Gary Struhl p. 95 Antonio Garcia-Bellido p. 98 William McGinnis p. 122 Matthew Scott p. 125 Cliff Tabin p. 142 Gerd Jürgens p. 168 Enrico Coen p. 183 Elliott Meyerowitz p. 184 Marty Yanofsky p. 190 Preface I undertook writing The Coiled Spring because now is an opportune time to provide the general science reader with an account of the rapidly unfolding field of developmental biology. Several factors con- tribute to this timeliness. First, the field is at the point where many of the general principles are well understood. This is by no means to say that we have answered all of the interesting questions. Quite to the contrary, many exciting discoveries remain to be made. But we do have a good idea about the outline of how development works, and this emerging story should be of significant interest to anyone curious to know how a fertilized egg smaller than the head of a pin makes a per- son, a fly, or a plant. One of the most unexpected and profound find- ings of the field has been the discovery that the basic mechanisms guid- ing development are the same in apparently disparate organisms such as flies and humans. Another reason for bringing the field of development to the atten- tion of a more general audience at this point is that our new understanding of developmental mechanisms is already beginning to have a great impact on the world in which we live. As a result, a basic knowledge of this field is important for all who are interested in shaping our common future. I hope this book will serve its intended purpose by fa- miliarizing the reader with classic experiments in developmental biology, some of the cutting-edge research that explains these classic ob- servations in simple mechanistic terms, and the implications of these discoveries for the future. Many people have contributed to this book. First, there are all of the scientists in the field of developmental biology from the time of Goethe to the present. In addition to the many investigators working actively on topics covered in this book, there are yet greater numbers of impassioned scientists who work long into the night hours to unravel many other equally interesting mysteries about development. These latter topics have not been discussed in this book only because of space limitations. I am particularly indebted to colleagues whom I pestered mercilessly with questions about their fields, including Marty Yanofsky, Detlef Weigel, Kathy Barton, Laurie Smith, Phil Benfey, and David Kimelman. I also express my gratitude to those who kindly (cid:2) xi(cid:2) xii (cid:2) Preface agreed to be featured in the short biographical sketches scattered throughout the text. The “biobox” subjects were all asked to respond to a set of similar questions, and, invariably, they gave insightful and heartfelt responses. For me, reading and then organizing the comments of these accomplished individuals was one of the most interesting and rewarding parts of writing this book. The single most obvious outcome of this query was that questions such as “What are the most important ingredients in scientific discovery?” evoked a wide range of opinions and commentary. The diversity of views on such topics underscores the fact that scientists are individuals and approach science from many different perspectives, employing a variety of distinct strategies and styles. There may be more ways to study embryos than there are ways for embryos to develop! I also thank the scientific reviewers of this book who took the time to make valuable and critical comments on the first draft of the book. In addition, I thank my father Jesse Bier; my colleagues at the University of California, San Diego; Marty Yanofsky, Bill McGinnis, Randall Johnson, Georgiana Zimm, Larry Reiter, and Diane Ingles; and Detlef Weigel of the Salk Institute, for reading drafts of the book or var- ious chapters and making insightful comments. These reviewers helped define the focus and made excellent suggestions about the organization of topics. Thanks are also due to the people at Cold Spring Harbor Laboratory Press for their help, especially Inez Sialiano and Jan Argentine in the Development Department and Pat Barker and Denise Weiss in the Production Department. Likewise, I was fortunate to have the assistance of Meghan Scott, a dedicated UCSD undergraduate, who helped compile the glossary. I also thank Dan Ang, who put in many hours preparing the plates of original data, and members of my lab for putting up with this project. Most of all, I thank Judy Cuddihy, my tire- less, good-natured editor at Cold Spring Harbor Laboratory Press, and friend, for all of her varied efforts and encouragement during the lengthy series of steps from start to finish on the book. Finally, I am most grateful to my wife Kathryn Burton and close friend Marty Yanofsky for their constant encouragement and support during the course of conceiving and writing this book. I’m sure they are quite happy that the ordeal is over and that the coiled spring has sprung!