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"The rich scientific knowledge about the genetic basis of life and it complex involvement in the life of individuals and populations is highly relevant to our worldview. "Genes in Development "helps to bring understandings of the conceptual and philosophical implications of molecular genetics up to date."--Werner Arber, Nobel Laureate in Medicine and Emeritus Professor of Molecular Microbiology, University of Basel

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Genes in Development

Duke University Press

Contents

Introduction EVA M. NEUMANN-HELD AND CHRISTOPH REHMANN-SUTTER.............................................................................11 Genome Analysis and Developmental Biology: The Nematode Caenorhabditis elegans as a Model System THOMAS R. BRGLIN......................152 Genes and Form: Inherency in the Evolution of Developmental Mechanisms STUART A. NEWMAN AND GERD B. MLLER..............................383 From Genes as Determinants to DNA as Resource: Historical Notes on Development and Genetics SAHOTRA SARKAR..............................774 The Origin of Species: A Structuralist Approach GERRY WEBSTER AND BRIAN C. GOODWIN......................................................995 On the Problem of the Molecular versus the Organismic Approach in Biology ULRICH WOLF...................................................1356 Genes, Development, and Semiosis JESPER HOFFMEYER.......................................................................................1527 The Fearless Vampire Conservator: Philip Kitcher, Genetic Determinism, and the Informational Gene PAUL E. GRIFFITHS.....................1758 Genetics from an Evolutionary Process Perspective JAMES GRIESEMER.......................................................................1999 Genes-Causes-Codes: Deciphering DNA's Ontological Privilege EVA M. NEUMANN-HELD.........................................................23810 Boundaries and (Constructive) Interaction SUSAN OYAMA..................................................................................27211 Beyond the Gene but Beneath the Skin EVELYN FOX KELLER.................................................................................29012 Poiesis and Praxis: Two Modes of Understanding Development CHRISTOPH REHMANN-SUTTER....................................................31313 Developmental Emergence, Genes, and Responsible Science BRIAN C. GOODWIN...............................................................33714 Nothing Like a Gene JACKIE LEACH SCULLY................................................................................................349Contributors...............................................................................................................................365Index......................................................................................................................................369

Chapter One

The Nematode Caenorhabditis elegans as a Model System

THOMAS R. BRGLIN

A general and basic tenet of scientific research is to simplify a complex problem to smaller, more tractable units that can be studied and unraveled. Depending on the biological question, scientists choose particular organisms as model systems. Each model provides researchers with particular biological or experimental advantages that help them in their quest to understand fundamental biological principles and problems. In 1963 Sydney Brenner wanted to proceed from bacterial and viral genetics to a more complex, multicellular animal. He proposed studying a small nematode that he thought would be eminently suitable for investigating many aspects of cell and nervous system development. After careful deliberation he chose Caenorhabditis elegans, and with this model he succeeded in establishing a whole new research field. As a result, "founding father" Sydney Brenner and two other C. elegans researchers, John Sulston and Bob Horvitz, were awarded the Nobel Prize in Physiology or Medicine in 2002. John Sulston made key contributions to elucidating the C. elegans cell lineage as well as to its genome project, and Bob Horvitz contributed significantly to the understanding of programmed cell death. I became attracted to this model system because of its elegance and other advantages I will outline below.

The little worm will serve here as an introduction to how researchers study genes and understand their function in the context of a living organism. This chapter will first introduce the advantages of the C. elegans model system (see also the key textbooks by Wood [1988] and Riddle et al. [1997]), and then will proceed to the C. elegans genome, where the principle of gene function via proteins is introduced (for a key textbook on molecular biology, see Alberts et al. 2002). Subsequently, I will talk about a particular group of genes that regulate other genes-the homeobox genes-and demonstrate how we study the function of particular genes in the worm. I hope that this exposition will remove at least some of the mystical connotations that the term gene has acquired in recent times and reveal the true beauty of the gene and the genome.

The Biology of Caenorhabditis elegans

C. elegans belongs to a group of animals called nematodes. Nematodes are roundworms or threadworms with smooth-skinned, unsegmented, long-cylindrical bodies. There are both free-living and parasitic forms, and they can be found in both aquatic and terrestrial environments. Quite a number of parasitic nematodes are known to afflict human beings: it has been estimated that as much as 25 percent of the world's population is infected by some type of parasitic nematode. C. elegans is a small, free-living nematode found in temperate regions in the soil, where it feeds on bacteria (fig. 1).There are two sexes: self-fertilizing hermaphrodite animals and male animals. Both are small, the adult hermaphrodite being a little larger and reaching a size of 1.2 mm when fully grown.

Because of its small size and simple food requirements, C. elegans can be easily reared in the laboratory on agar plates seeded with a lawn of bacteria such as Escherichia coli. The life cycle of C. elegans is extremely fast: it takes only about three days from the time a young adult starts to lay eggs until the next generation has grown and starts laying its own eggs. Development proceeds through several stages: embryogenesis, four larval stages (termed L1, L2, L3, and L4), and the adult stage. This extremely rapid reproductive rate is unique among multicellular animals. Each hermaphrodite animal can produce up to three hundred offspring, so a single animal on an agar plate can produce thousands of first- and second-generation offspring in about a week. C. elegans is thus an ideal model system for genetic studies because a large number of offspring can be analyzed in a very short time.

Apart from easy maintenance, small size, and fast and plentiful reproduction, C. elegans offers many other advantages that have made it an excellent model system for modern biologists. In part because of their small size, the embryos, larvae, and adult animals are transparent when viewed under a microscope, allowing researchers to identify all the different cells (in fact, the cell nuclei) and making it possible to follow the cell divisions of embryo-genesis and larval development. The fact that the cell division patterns are remarkably reproducible from embryo to embryo permitted John Sulston and his co-workers to establish the complete cell lineage for C. elegans. That means we know exactly how each cell divides during development, what...