The Retinoids

Pascal Dollé, M.D., Ph.D., is Team Leader and Department Head at the Institute of Genetics and Molecular and Cellular Biology (IGBMC), Illkirch, France Karen Niederreither, Ph.D, is an Associate Professor at the University of Strasbourg, School of Dentistry in Strasbourg, France, and performs research at the IGBMC, Illkirch, France

Contributors ix

Preface xiii

Part I: Vitamin A metabolic and enzymatic pathways 1

1 Vitamin a Metabolism, Storage and Tissue Delivery Mechanisms 3
William S. Blaner and Yang Li

2 Assimilation and Conversion of Dietary Vitamin a into Bioactive Retinoids 35
Earl H. Harrison and Carlo dela Senã’s

3 Intracellular Storage and Metabolic Activation of Retinoids: Lipid Droplets 57
Joseph L. Napoli and Charles R. Krois

4 Evolution of the Retinoic Acid Signaling Pathway 75
Vincent Laudet, Elisabeth Zieger, and Michael Schubert

Part II: Biochemistry and cellular biology of retinoic acid signaling 91

5 Control of Gene Expression by Nuclear Retinoic Acid Receptors: Post-Translational And Epigenetic Regulatory Mechanisms 93
Marilyn Carrier and Cécile Rochette-Egly

6 Retinoic Acid Receptor Coregulators in Epigenetic Regulation of Target Genes 117
Li-Na Wei

7 Retinoid Receptors: Protein Structure, Dna Recognition and Structure–Function Relationships 131
William Bourguet and Dino Moras

8 How the RAR–RXR Heterodimer Recognizes the Genome 151
Sylvia Urban, Tao Ye, and Irwin Davidson

9 Retinoid Receptor-Selective Modulators: Chemistry, 3D Structures and Systems Biology 165
Marco-Antonio Mendoza-Parra, William Bourguet, Angel R. de Lera, and Hinrich Gronemeyer

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 193
Marcia I. Dawson and Zebin Xia

11 The Dual Transcriptional Activity of Retinoic Acid 273
Noa Noy

12 Retinoids, epigenetic changes during stem cell differentiation, and cell lineage choice 291
Lorraine J. Gudas

Part III: RETINOIC ACID SIGNALING IN DEVELOPMENT 307

13 Retinoic Acid Signaling and Central Nervous System Development 309
Malcolm Maden

14 The Role of Retinoic Acid in Limb Development 339
Gregg Duester

15 Retinoic Acid Signaling and Heart Development 353
Stéphane Zaffran and Karen Niederreither

16 Retinoic Acid in the Developing Lung and Other Foregut Derivatives 371
Wellington V. Cardoso and Felicia Chen

17 Retinoic Acid and the Control of Meiotic Initiation 383
Josephine Bowles and Peter Koopman

Part IV: RETINOIDS AND PHYSIOLOGICAL FUNCTIONS 401

18 Retinoids and the Visual Cycle: New Actors for an “OLD” Function 403
Darwin Babino and Johannes von Lintig

19 Retinoid Signaling in the Central Nervous System 421
Peter McCaffery and Wojciech Krężel

20 Retinoid Turnover and Catabolism: Influences of Diet and Inflammation 449
A. Catharine Ross and Reza Zolfaghari

21 Retinoids and the Immune System 465
J. Rodrigo Mora and Makoto Iwata

22 Retinoic Acid Receptor Signaling in Post-Natal Male Germ Cell Differentiation 485
Manuel Mark and Norbert B. Ghyselinck

Part V: RETINOIDS, DISEASE AND THERAPY 505

23 Epidemiology and Prevention of Vitamin a Deficiency Disorders 507
Keith P. West, Jr.

24 Retinoid Pathway Gene Mutations and the Pathophysiology Of Related Visual Diseases 529
Yaroslav Tsybovsky and Krzysztof Palczewski

25 Retinoic Acid in Acute Myeloid Leukemias 543
Hugues de Thé and Pierre Fenaux

26 Advances in the Use of Retinoids in Cancer Therapy and Prevention 557
Michael J. Spinella, Sarah J. Freemantle, and Ethan Dmitrovsky

Index 575