T-box Genes in Development and Disease

Chapter One: Evolution and Classification of the T-Box Transcription Factor Family

• Abstract
• 1 An Updated Phylogenetic Classification of the T-Box Gene Family
• 2 Premetazoan T-Box Genes
• 3 Metazoan T-Box Classes and Function
• 4 Functional Conservation of Premetazoan and Early-Metazoan Brachyury Homologs
• 5 Ancestral Conserved Role of Brachyury in Morphogenetic Movements
• 6 The Evolution of T-Box Regulation
• Acknowledgments

Chapter Two: The Remarkably Diverse Family of T-Box Factors in Caenorhabditis elegans

• Abstract
• 1 Introduction
• 2 T-Box Genes in C. elegans and Related Nematodes
• 3 DNA-Binding Specificity of C. elegans T-Box Factors
• 4 Genetic Analyses of T-Box Factor Function in C. elegans
• 5 Posttranslational Mechanisms Affecting T-Box Factor Activity
• 6 Concluding Remarks
• Acknowledgments

Chapter Three: T-Box Genes and Developmental Gene Regulatory Networks in Ascidians

• Abstract
• 1 Introduction
• 2 Brachyury and the Temporal Control of Notochord Specification, Development, and Differentiation
• 3 Tbx2/3: An Essential Mediator of Brachyury Function in the Notochord
• 4 The Lineage-Specific Duplication of Tbx6 Genes in Ascidians
• 5 Tbx6a
• 6 Tbx6b, Tbx6c, and the Interpretation of the Maternally Inherited Muscle Determinant
• 7 Tbx6b and Tbx6c in Heart Development
• 8 Tbx1/10 and the Evolutionary Origins of the Pharyngeal Muscles
• 9 Tbx15/18/22 (VegTR) and the Establishment of Muscle Cell Identity
• 10 Maternal T and Tail Development
• 11 Tbx20: In or Out of the Ascidian Heart?
• 12 Transcriptional Regulation of T-Box Genes Expression
• 13 Concluding Remarks
• Acknowledgments

Chapter Four: Eomesodermin—At Dawn of Cell Fate Decisions During Early Embryogenesis

• Abstract
• 1 Introduction
• 2 Early Eomes Functions in the Trophectoderm
• 3 Eomes in the Visceral Endoderm Promotes Formation of the Embryonic AP Axis
• 4 Eomes Functions During the Formation of Germ Layers
• 5 Eomes Transcriptional Activities During Germ Layer Formation
• 6 Control of Eomes Expression During Gastrulation Onset
• Acknowledgments

Chapter Five: Cooperation Between T-Box Factors Regulates the Continuous Segregation of Germ Layers During Vertebrate Embryogenesis

• Abstract
• 1 Controversy of Germ Layer Segregation: Holmdahl's Blastema vs Vogt's Predetermination Model
• 2 Multiple Functions of T-Box Factors in Development and Disease
• 3 Early Embryonic Roles of T-Box Factors in Segregating and Differentiating Germ Layers in Vertebrates
• 4 Implications for Reverse Engineering ES Cells
• 5 Summary
• Acknowledgments

Chapter Six: T-Box Genes in Drosophila Mesoderm Development

• Abstract
• 1 Introduction
• 2 T-Box Genes in Visceral and Gonadal Mesoderm Development
• 3 T-Box Genes in Drosophila Cardiogenesis
• 4 The Roles of the Drosophila Orthologs of Tbx1 (org-1) and Tbx20 (mid and H15) During Embryonic Somatic Muscle Assignments
• 5 The Role of Drosophila Tbx1 (org-1) in Lineage Plasticity, Reprogramming, and Commitment During Adult Myogenesis
• 6 Concluding Remarks and Outlook
• Acknowledgments

Chapter Seven: TBX5: A Key Regulator of Heart Development

• Abstract
• 1 TBX5, a Member of the T-Box Family of Transcription Factors
• 2 TBX5 Expression
• 3 TBX5 Haploinsufficiency: Holt–Oram Syndrome
• 4 Animal Model of Holt–Oram Syndrome
• 5 TBX5 in Cardiac Morphologic Development
• 6 TBX5 in Cardiac Conduction System Development
• 7 Homozygous Tbx5 Mutations Reveal Novel Roles of TBX5
• 8 The TBX5 Gene Regulatory Network
• 9 Concluding Remarks

Chapter Eight: Tbx1: Transcriptional and Developmental Functions

• Abstract
• 1 Tbx1: Structure and Function(s)
• 2 Developmental Functions
• 3 Concluding Remarks and Future Perspectives
• Acknowledgment

Chapter Nine: T-Box Genes in the Kidney and Urinary Tract

• Abstract
• 1 Introduction
• 2 T-Box Genes, an Evolutionary Conserved Family of Developmental Regulators
• 3 Tbx18 in Ureter and Kidney Development
• 4 Tbx1 in Kidney Development
• 5 Tbx20 in Bladder/Cloacal Development
• 6 Tbx2 and Tbx3, a Closely Related Pair of T-Box Transcription Factor Genes in Kidney and Bladder Development
• 7 Conclusion and Outlook
• Acknowledgment

Chapter Ten: Control of Neuronal Development by T-Box Genes in the Brain

• Abstract
• 1 Discovery of T-Box Gene Expression in the Developing Brain and Neural Retina
• 2 Expression of Tbr1 Subfamily T-Box Genes in Brain and Neural Retina
• 3 Functions of Tbr1 Subfamily T-Box Genes in Brain and Neural Retina
• 4 Regulation of T-Box Genes
• 5 Downstream Target Genes Regulated by T-Box Genes in Cerebral Cortex
• 6 Human Disorders Caused by T-Box Gene Mutations in Brain
• 7 Summary
• Acknowledgment

Chapter Eleven: T-Box Genes in Drosophila Limb Development

• Abstract
• 1 Orthology Between Drosophila and Mammalian Tbx Genes
• 2 Embryonic Origin of the Drosophila Limb Imaginal Discs: The Role of Doc
• 3 Pattern Formation in the Larval Leg Disc
• 4 Tbx Genes in Drosophila Leg Development
• 5 Pattern Formation and Proliferation Control in the Larval Wing Disc
• 6 Tbx Genes in Drosophila Wing Development
• 7 Tbx Gene Function in Haltere Development
• 8 Conclusion
• Acknowledgments

Chapter Twelve: The Roles of T-Box Genes in Vertebrate Limb Development

• Abstract
• 1 Introduction
• 2 The Tbx2/3/4/5 Subfamily Members Are Significant Players in Limb Development
• 3 The Paralogous T-Box Genes, Tbx2 and Tbx3 Have Distinct Functions During Limb Development
• 4 Tbx4 and Tbx5, The Markers of the Hindlimb and Forelimb
• 5 Tbx1 Family Members Have Functions in Limb Chondrogenic Precursors
• 6 Brachyury (T) Has a Role in AER Maturation
• 7 Eomes (Tbr2), a Marker for Digit 4
• 8 Future Perspectives

Chapter Thirteen: T-Box Genes in Human Development and Disease

• Abstract
• 1 Introduction
• 2 T (Brachyury)/Chordoma
• 3 TBX1/22q11.2 Deletion Syndrome (DiGeorge Syndrome/Velocardiofacial Syndrome)
• 4 TBX3/Ulnar–Mammary Syndrome
• 5 TBX4/Small Patella Syndrome
• 6 TBX5/Holt–Oram Syndrome/CHD
• 7 TBX6/Spondylocostal Dysostosis
• 8 TBX15/Cousin Syndrome
• 9 TBX19/Isolated ACTH Deficiency
• 10 TBX20/Congenital Heart Disease
• 11 TBX22/Cleft Palate With or Without Ankyloglossia, X-Linked (CPX)
• 12 Concluding Remarks
• Acknowledgment