Table Of ContentThe 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.
QH453 .B53 2000
571.8(cid:2)5—dc21 00-022975
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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 devel-
opmental biology is described using examples of the Gurdon ex-
periment, which proved that all cells in a frog contain the same ge-
netic 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 devel-
oping 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 differ-
ent 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 devel-
opment 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 similar-
ities 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 hu-
mans 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 impli-
cations 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 developmen-
tal 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 under-
standing of developmental mechanisms is already beginning to have a
great impact on the world in which we live. As a result, a basic knowl-
edge 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 biol-
ogy, 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 or-
ganization 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!