Beschreibung
Having received the invitation from Springer-Verlag to produce a volume on drug-induced birth defects for the Handbook of Experimental Pharmacology, we asked ourselves what new approach could we offer that would capture the state of the science and bring a new synthesis of the information on this topic to the world's literature. We chose a three-pronged approach, centered around those particular drugs for which we have a relatively well established basis for understanding how they exert their unwanted effects on the human embryo. We then supplemented this information with a series of reviews of critical biological processes involved in the established normal developmental patterns, with emphasis on what happens to the embryo when the processes are perturbed by experimental means. Knowing that the search for mechanisms in teratology has often been inhibited by the lack of understanding of how normal development proceeds, we also included chapters describing the amazing new discoveries related to the molecular control of normal morphogenesis for several organ systems in the hope that the experimental toxicologists and molecular biologists will begin to better appreciate each others questions and progress. Several times during the last two years of developing outlines, issuing invitations, reviewing chapters, and cajoling belated contributors, we have wondered whether we made the correct decision to undertake this effort.
Autorenporträt
Inhaltsangabe1 Introduction.- Section I: Recent Advances in Understanding Normal Development at the Biochemical and Molecular Level.- 2 Cardiac Morphogenesis: Formation and Septation of the Primary Heart Tube.- A. Introduction.- B. Establishing Heart-Forming Primordia.- I. Commitment to the Heart Lineage.- II. Formation of the Heart-Forming Fields.- III. Segregation of Lineage Within the Heart Fields.- IV. Molecular Regulation of the Cardiomyogenic Lineage.- V. Regulation of the Endocardial Lineage.- VI. Fate of the Heart Fields.- C. Morphogenesis of the Primary Heart Tube.- I. Elongation and Segmentation of the Tubular Heart.- II. Morphology of the Primitive Segments.- III. Developmental Fate of the Primitive Segments.- 1. Atrium.- 2. Ventricles.- 3. Atrioventricular Canal and Conotruncus.- D. Septation and Remodeling of the Tubular Heart into Four Chambers.- I. Looping.- II. Integration of Septal Primordia into Adult Partitions.- E. Conclusion.- References.- 3 Vertebrate Limb Development.- A. Introduction.- B. Developmental Anatomy of the Limb.- C. Pattern Regulation.- I. The Apical Ectodermal Ridge and Fibroblast Growth Factors.- II. The Zone of Polarizing Activity and the Supernumerary Response.- III. Sonic Hedgehog and Zone of Polarizing Activity Signaling.- IV. Regulation of Zone of Polarizing Activity Signaling/Sonic Hedgehog Expression.- V. Retinoic Acid and the Zone of Polarizing Activity Signal.- D. Homeobox-Containing Genes and Positional Information.- E. Digit Morphogenesis.- F. Conclusions.- References.- 4 Axial Skeleton.- A. Introduction.- B. Morphogenesis.- I. Formation of the Primitive Streak and the Notochord.- II. Segmentation of the Paraxial Mesoderm into Somites.- III. Differentiation of Somites into Dermomyotome and Sclerotome.- IV. From Sclerotomes to Mesenchymal Prevertebrae.- V. Chondrification of Prevertebrae.- VI. Ossification of Prevertebrae.- C. Genes Involved in Axial Skeleton Formation.- I. Gastrulation and Formation of Paraxial Mesoderm.- 1. Growth Factors, Signaling Molecules, and Their Receptors.- 2. Transcription Factors.- II. Segmentation of the Paraxial Mesoderm into Somites.- 1. Intercellular Signaling.- 2. Cell Adhesion.- 3. Extracellular Matrix Components.- 4. Transcription Factors.- III. Patterning of Somites.- 1. Craniocaudal Patterning: Cranial and Caudal Somite Halves.- 2. Dorsoventral Patterning.- a) Signaling Molecule Sonic Hedgehog.- b) Interpretation of the Inductive Sonic Hedgehog Signal: Transcription Factors of the Pax Gene Family.- c) Connection Between the Inductive Sonic Hedgehog Signal and the Nuclear Response Mediated by Pax Genes: Signal Transduction Via Cyclic Adenosine Monophosphate-Dependent Protein Kinases.- IV. Further Development of the Somite Compartments.- V. Regionalization Along the Craniocaudal Axis and Hox Genes.- VI. Local Control of Bone Shape During Embryogenesis and Growth.- 1. Bone Morphogenetic Proteins.- 2. Fibroblast Growth Factors and Their Receptors.- 3. Parathyroid Hormone-Related Peptide.- VII. Collagens and the Extracellular Matrix.- VIII. Regulation of Bone Maintenance and Bone Remodeling: Osteopetrosis and Osteoporosis.- IX. Influence of Teratogens on Axial Skeleton Development.- References.- 5 Molecular Mechanisms Regulating the Early Development of the Vertebrate Nervous System.- A. Early Development of the Nervous System.- B. Neurogenesis: The Role of the Helix-Loop-Helix Proneural Genes.- C. Establishing Identities Along the Anterior-Posterior Axis.- D. Segmentation and Patterning of the Hindbrain.- E. Generation of the Midbrain-Hindbrain Junction: The Role of Wnt1, En1 and Pax2.- F. Dorsoventral Patterning: The Opposing Roles of Sonic Hedgehog and BMPs.- References.- 6 Genetic Control of Kidney Morphogenesis.- A. Kidney Development as a Paradigm for Organogenesis.- B. Experimental Approaches for Studying Kidney Morphogenesis.- I. Transfilter Recombination System.- II. Genetic Analysis of Nephrogenesis Using Knockout, Transgenic, and Spontaneous Mouse Mu
