Title Page -- Copyright Page -- Contents -- Contributors -- Preface -- Part I Vitamin A Metabolic and Enzymatic Pathways -- Chapter 1 Vitamin A Metabolism, Storage and Tissue Delivery Mechanisms -- I. Introduction -- II. Vitamin A Metabolism Relevant to its Storage -- III. Vitamin A Storage -- IV. Vitamin A Transport in the Circulation -- V. Integration within the Intact Organism of Vitamin A Metabolism, Storage and Transport -- Acknowledgments -- References -- Chapter 2 Assimilation and Conversion of Dietary Vitamin A into Bioactive Retinoids -- I. Introduction -- II. Dietary Sources of Vitamin A and Provitamin A Carotenoids -- III. Intestinal Absorption and Metabolism of Dietary Vitamin A and Provitamin A Carotenoids -- IV. Formation of β-Apocarotenoids -- V. Possible Biological Functions of Apocarotenoids -- VI. Conclusions and Perspectives -- Acknowledgments -- References -- Chapter 3 Intracellular Storage and Metabolic Activation of Retinoids: Lipid Droplets -- I. Introduction -- II. Multilocular Lipid Droplets -- III. The Mitochondrial-Associated Membrane -- IV. Birth of Lipid Droplets -- V. Lipid Droplets and Retinoid Homeostasis -- VI. In the Absence of Lipid Droplets, LRAT and RDH1 Localize with the ER, Whereas CRBP1 and RDH10 Localize with Mitotracker -- VII. During Acyl Ester Biosynthesis LRAT, CRBP1 and RDH10 Associate with LIPID Droplets -- VIII. Lipid Droplet Association Activates RDH10 -- IX. Lipid Droplet Association Requires the N-termini of LRAT and RDH10 -- X. Summary -- XI. Conclusions and Future Directions -- References -- Chapter 4 Evolution of the Retinoic Acid Signaling Pathway -- I. Introduction -- II. An Overview of Chordate Retinoid Metabolism -- III. Retinoic Acid Signaling in Chordates -- IV. Evolution of Retinoic Acid Signaling -- V. Conclusions -- Acknowledgments -- References.

Part II Biochemistry and Cellular Biology of Retinoic Acid Signaling -- Chapter 5 Control of Gene Expression by Nuclear Retinoic Acid Receptors: Post-Translational and Epigenetic Regulatory Mechanisms -- I. Introduction -- II. The Basics of Rar Structure -- III. Repressive Epigenetic Landscape of Rar Target Genes in the Absence of Retinoic Acid -- IV. Reorganization of the Epigenetic Landscape after Retinoic Acid Addition -- V. Noncoding RNAs in the Regulation of the Epigenetic Landscape -- VI. Back to a Repressive Epigenetic Landscape when Transcription Turns "OFF" -- VII. Phosphorylation: Another Post-Translational Modification Code Induced by Retinoic Acid -- VIII. Two Models for the Activation of RAR Target Genes Via a Sea of Post-Translational Modifications and Epigenetic Changes -- IX. Aberrant Epigenics in Cancer: Consequences on the Retinoic Acid Response -- X. Conclusion and Future Prospects -- References -- Chapter 6 Retinoic Acid Receptor Coregulators in Epigenetic Regulation of Target Genes -- I. Introduction -- II. Coregulators OF RARs and RXRs -- III. Coregulators in Epigenetic Regulation -- IV. The Future -- Acknowledgments -- References -- Chapter 7 Retinoid Receptors: Protein Structure, DNA Recognition and Structure-Function Relationships -- I. Introduction -- II. General Organization of Retinoid Receptors -- III. Structure of Full-Length RAR-RXR-DNA Complexes -- IV. Coregulator Binding -- V. Structural Basis for Allosteric Control Mechanisms of Cofactor Binding -- VI. Conclusions -- References -- Chapter 8 How the RAR-RXR Heterodimer Recognizes the Genome -- I. Introduction -- II. Hormone Response Elements -- III. VDR and TR Occupy DR3 and DR4 Elements in Cultured Cells -- IV. PPAR and LXR Prefer Nonconsensus Elements -- V. Genomic Binding of the RAR-RXR Heterodimer -- VI. Summary and Conclusions -- Acknowledgments -- References.

Chapter 9 Retinoid Receptor-Selective Modulators: Chemistry, 3D Structures and Systems Biology -- I. Introduction -- II. RXR Versus RAR Selectivity as a Function of the Ligand-Binding Pocket Architectures -- III. Systems Biology of Retinoid Action -- IV. Conclusions -- Acknowledgments -- References -- Chapter 10 Use of Retinoid Receptor Ligands to Identify Other Nuclear Receptor Ligands: Retinoid-Related Molecules are Ligands for the Small Heterodimer Partner (SHP) "Orphan" Receptor -- I. Introduction -- II. Nuclear Receptor and Ligand Similarities -- III. Apoptosis Induction by AHPN -- IV. Structure-Activity Relationship Studies Leading to a Preclinical Candidate -- V. Identification of Small Heterodimer Partner (SHP) as a Retinoid-Related Molecule (RRM) Target -- VI. Small Heterodimer Partner Structure and Function -- VII. Construction of a Small Heterodimer Partner Model to Facilitate Ligand Design -- VIII. Retinoid-Related Molecule Mechanism of Action Studies -- IX. Additional Targets of Retinoid-Related Molecules -- X. Retinoid-Related Molecule Mechanism of Action Studies by Other Groups -- XI. Investigations on the Mechanism of Action of Small Heterodimer Partner in the Absence of an Added Retinoid-Related Molecule -- References -- Chapter 11 The Dual Transcriptional Activity of Retinoic Acid -- I. Retinoic Acid Receptors: PPARβ/δ Joins Rars -- II. Retinoic Acid-Binding Proteins: CRABP2 and FABP5 Cooperate with RAR and PPARβ/δ -- III. Biological Activities of Retinoic Acid Critically Rely on Precise Balance between its Dual Transcriptional Pathways -- IV. Conclusions -- Acknowledgments -- References -- Chapter 12 Retinoids, Epigenetic Changes During Stem Cell Differentiation, and Cell Lineage Choice -- I. Introduction -- II. Retinoic Acid Signaling is Associated with Transcriptional Activation and Epigenetic Changes in Stem Cells.

III. Retinoids and Epigenetic Modifications -- IV. Retinoic Acid and the Differentiation of Embryonic Stem Cells Along Various Lineages: Six Examples -- V. Determinants of the Stability of the Differentiated Phenotype -- VI. Summary and Future Directions -- Acknowledgments -- References -- Part III Retinoic Acid Signaling in Development -- Chapter 13 Retinoic Acid Signaling and Central Nervous System Development -- I. Introduction -- II. The Beginning of Retinoic Acid Signaling at Early Node Stages (Figure 13.1A, hn) -- III. Retinoic Acid Signaling as the Neural Plate Forms and Undergoes Anteroposterior Patterning (Figure 13.1B, np) -- IV. Hindbrain Specification (Figure 13.1C, hb) -- V. The Hindbrain Gradient of Retinoic Acid (Figure 13.1C, hb) -- VI. Spinal Cord Formation and Patterning at the Posterior End of the Embryo (Figure 13.1C, 13.1D, cs) -- VII. Dorsoventral Patterning in the Spinal Cord and Motor Neuron Specification (Figure 13.1D, sc) -- VIII. Return to the Front of the Embryo: Outgrowth of the Telencephalon (Figure 13.1E, fn) -- IX. Olfactory Development (Figure 13.1E, olf) -- X. The Eye (Figure 13.1E, 13.1F) -- XI. Patterning Within the Telencephalon: The Lateral Ganglionic Eminence (Figure 13.1F, lge) -- XII. The Later Hindbrain and Cortex (Figure 13.1F) -- XIII. Conclusion -- References -- Chapter 14 The Role of Retinoic Acid in Limb Development -- I. Introduction -- II. Enzymes and Receptors for Retinoic Acid Synthesis and Signaling -- III. Genetic Models for Investigation of Retinoic Acid Function During Limb Development -- IV. Retinoic Acid is not Required for Limb Axial Patterning -- V. Forelimb Induction Requires Retinoic Acid Signaling -- VI. Retinoic Acid is Required for Interdigital Development -- VII. Conclusions -- Acknowledgments -- References -- Chapter 15 Retinoic Acid Signaling and Heart Development -- I. Introduction.

II. Early Functions in Formation and Patterning of the Second Heart Field -- III. The Epicardium: A Source of Ra-Regulated Signals Controlling Myocardial Cell Proliferation and Differentiation -- IV. Actions on Progenitor Cell Populations -- V. Interactions with Other Signaling Pathways: Clues to Congenital Malformations -- VI. Conclusions and Perspectives -- Acknowledgments -- References -- Chapter 16 Retinoic Acid in the Developing Lung and Other Foregut Derivatives -- I. Introduction -- II. From Patterning of the Foregut to Lung Development -- III. Retinoic Acid Signaling Controls a Gene Network Crucial for Early Lung Development -- IV. Involvement of Retinoic Acid in Branching Morphogenesis and Lung Epithelial Differentiation -- V. Other Functions of Retinoic Acid in Lung Development -- VI. Retinoic Acid in Postnatal Lung Development and Lung Repair -- VII. Distinct Roles for Retinoic Acid in Organogenesis of Other Foregut Derivatives -- VIII. Conclusions -- Acknowledgments -- References -- Chapter 17 Retinoic Acid and the Control of Meiotic Initiation -- I. Introduction -- II. Germ Cells and Meiosis -- III. A Role for Retinoic Acid in Initiating Meiosis in the Fetal Ovary -- IV. What is the Source of Retinoic Acid in the Ovary? -- V. What About Meiosis in the Testis? -- VI. Retinoic Acid Triggers Meiosis in a Range of Vertebrates -- VII. Why do Only Germ Cells Respond to Retinoic acid by Upregulating Stra8? -- VIII. Is there Sufficient Retinoic Acid in the Mouse Fetal Ovary to Trigger Stra8 Expression? -- IX. Other Factors Involved in Induction of Meiosis in the Fetal Gonad -- X. Conclusions -- References -- Part IV Retinoids and Physiological Functions -- Chapter 18 Retinoids and the Visual Cycle: New Actors for an "Old" Function -- I. Introduction -- II. Carotenoid Cleaving Enzymes -- III. Absorption and Transport of Chromophore Precursors.

IV. The "Canonical" Visual Cycle.