Note: Front Cover -- Vertebrate Skeletal Development -- Copyright -- Contents -- Contributors -- Preface -- Chapter One: Stem and progenitor cells in skeletal development -- 1. Introduction -- 2. Colony-forming unit fibroblasts (CFU-Fs) and mesenchymal/skeletal stem cells (MSCs/SSCs): A traditional definition for ... -- 3. How relevant are CFU-Fs and MSCs/SSCs to skeletal development? -- 4. In vivo lineage-tracing experiments in mice: An unambiguous approach to reveal cell fates -- 5. Endochondral bone development/Phase 1: Formation of the growth plate -- 6. Endochondral bone development/Phase 2: Formation of the perichondrium and osteoblast precursors -- 7. Endochondral bone development/Phase 3: Formation of the primary ossification center and the bone marrow cavity -- 8. Endochondral bone development/Phase 4: Formation of the postnatal growth plate and continued growth of the marrow space -- 9. Endochondral bone development/Phase 5: Establishment and maintenance of the adult bone marrow stroma -- 10. Periosteum and craniofacial sutures -- 11. Sox9 osteoblast precursors -- 12. Parathyroid hormone (PTH) action on skeletal precursors -- 13. Wnt/β-catenin signaling and cell fate decision -- 14. Conclusions and perspectives -- Acknowledgments -- References -- Chapter Two: ECM signaling in cartilage development and endochondral ossification -- 1. Introduction -- 2. Chondrogenesis and endochondral ossification -- 3. Roles of integrins in chondrogenesis and further chondrocyte maturation -- 4. Integrin downstream partners: Connecting ECM to the cell cytoskeleton -- 4.1. Focal adhesion kinase -- 4.2. Rho GTPases: Family members with different functions -- 4.3. MAP kinase cascade -- 5. Other non-integrin cell receptors -- 5.1. CD44 -- 5.2. Syndecan -- 5.3. Discoidin domain receptors -- 6. Conclusions and implications -- Acknowledgments -- References. , Chapter Three: Development of the axial skeleton and intervertebral disc -- 1. Introduction -- 2. Development of somite derived structures -- 2.1. Somitogenesis -- 2.2. Sclerotome specification -- 2.3. Resegmentation -- 2.4. Sclerotome derivatives -- 2.4.1. Vertebra -- 2.4.2. Annulus fibrosus -- 2.4.3. Tendon/ligament -- 3. Development of the nucleus pulposus from notochord -- 3.1. Formation and function of the notochord -- 3.1.1. Notochord sheath -- 3.2. Identification of notochordal and NP markers -- 3.3. Notochord-to-nucleus pulposus transition -- 3.4. Maintenance of the nucleus pulposus -- 4. Conclusions and implications -- Acknowledgments -- References -- Chapter Four: Regulatory mechanisms of jaw bone and tooth development -- 1. An overview of jaw bone and tooth development -- 2. Early development of the first pharyngeal arch -- 2.1. Cellular contributions to mandible and maxilla development -- 2.2. Molecular identity of the developing mandible and maxilla -- 3. Jaw bone development -- 3.1. Meckel´s cartilage -- 3.2. Mandibular bone osteogenesis -- 3.3. Hemifacial microsomia -- 3.4. Quantitative analysis using dynamic imaging and anatomical landmarks -- 4. Tooth development -- 4.1. Early interaction between odontogenic ectoderm and ectomesenchyme -- 4.2. Signaling regulating dentin and enamel formation -- 4.3. Tooth root development -- 4.4. Tooth and jaw bone interaction -- 4.5. Dental stem cells -- 5. Stem cells and regenerative therapies -- 5.1. Mandibular distraction osteogenesis, growth factors, and stem cell treatment -- 5.2. Dentin repair and regeneration -- 6. Conclusion and future directions -- Acknowledgments -- References -- Chapter Five: Joints in the appendicular skeleton: Developmental mechanisms and evolutionary influences -- 1. Introduction -- 2. Onset of limb synovial joint formation: The interzone. , 3. Interzone cell function and fate -- 4. Articular cartilage postnatal growth and morphogenesis -- 5. Evolutionary considerations -- 6. Conclusions and implications -- Acknowledgments -- References -- Chapter Six: BMPs, TGFβ, and border security at the interzone -- 1. Introduction -- 2. Overview of the BMP and TGFβ signaling pathways -- 3. Inhibition of BMP signaling in IZ cells is a critical step in joint formation -- 4. Genetic evidence that GDF5 has a role in joint formation -- 5. How does Gdf5 signaling direct joint formation? -- 6. TGFβ has a complex role in skeletal development -- 7. How might TGFβ signaling interfere with BMP signaling in the IZ? -- 8. Conclusions and future directions -- References -- Chapter Seven: Roles and regulation of SOX transcription factors in skeletogenesis -- 1. Introduction -- 2. Shared and distinctive features of SOX proteins -- 3. Skeletal dysmorphism due to SOX mutations -- 4. SOX genes and the control of skeletal progenitors -- 5. Roles of SOX genes in chondrogenesis -- 6. Roles of SOX genes in osteogenesis -- 7. Regulation of SOX genes and RNAs in skeletal cells -- 8. Post-translational regulation of SOX proteins in skeletal cells -- 9. Conclusions and perspectives -- Acknowledgments -- References -- Chapter Eight: Fibroblast growth factors in skeletal development -- 1. Fibroblast growth factor signaling pathways -- 2. FGF/FGFR expression -- 2.1. Expression of FGF and FGF receptors in the developing appendicularskeleton -- 2.2. Expression of FGF and FGF receptors in the developing axial skeleton -- 3. FGF signaling in growth plate chondrocytes -- 4. FGF signaling in cortical, trabecular, and intramembranous bone -- 4.1. FGFR signaling in osteoblasts -- 4.2. FGF interactions with other pathways -- 5. Mutations in FGFRs in human skeletal disease -- 5.1. Chondrodysplasia syndromes. , 5.2. Mouse models with mutations in Fgfr3 -- 5.3. FGFR signaling pathway-based therapeutic strategies -- 5.4. CATSHL syndrome (loss of function of Fgfr3) -- 5.5. Craniosynostosis syndromes -- 5.6. FGFR signaling and potential therapeutic strategies in craniosynostosis -- 6. Conclusions and perspectives -- Acknowledgments -- References -- Chapter Nine: Wnt-signaling in skeletal development -- 1. Introduction -- 1.1. Wnt-signaling -- 2. Wnt-signaling in endochondral bone formation -- 2.1. Roles of Wnt-signaling during the early steps of endochondral bone formation in the limbs -- 2.2. Effects of Wnt-signaling on proliferating chondrocytes -- 2.3. Wnt-signaling and growth plate functions -- 3. Role of Wnt signaling in osteoblast differentiation and osteoblast function -- 3.1. Wnt-signaling and osteocytes -- 4. Wnt signaling and osteoclastogenesis -- 5. Roles of Wnt-signaling in intramembranous bone formation -- 6. Wnt signaling in joint development, maintenance, and degeneration -- 7. Defects in Wnt-signaling associated with skeletal diseases -- 8. Conclusions and implications -- Acknowledgments -- References -- Chapter Ten: Gαs signaling in skeletal development, homeostasis and diseases -- 1. Introduction -- 2. Gαs signaling in human skeletal development and homeostasis -- 2.1. Skeletal diseases caused by activating mutations in the GNAS gene -- 2.2. Skeletal diseases caused by inactivating mutations in the GNAS gene -- 3. Regulation of osteoblast differentiation by Gαs signaling -- 3.1. Gαs in osteochondral progenitor cells -- 3.2. Gαs in the osteoblast lineage -- 3.3. Gαs in osteocyte lineage -- 3.4. Gαs in osteoclastogenesis -- 4. Cross talk of Gαs signaling with other signaling pathways in the skeletal system -- 4.1. Gαs is an inhibitor of Hedgehog signaling -- 4.2. Gαs signaling regulates bone through Wnt/β-catenin signaling. , 4.3. Gαs signaling and Hippo signaling -- 5. Mouse models of skeletal diseases caused by GNAS mutations -- 5.1. Mouse models of FD -- 5.1.1. Current treatment -- 5.2. POH mouse models -- 5.2.1. Current treatment options -- 6. Conclusions and implications -- Acknowledgments -- References -- Chapter Eleven: Importance of the circadian clock in tendon development -- 1. Introduction -- 2. Mammalian circadian clock -- 2.1. ``Master´´ clock -- 2.2. Cell autonomous molecular oscillator -- 3. Peripheral clocks -- 3.1. Tissue-specificity of peripheral clocks -- 3.2. Peripheral clock entrainment -- 3.3. Aging of peripheral clocks -- 4. Circadian clock regulation of tendon homeostasis -- 4.1. Tendon circadian transcriptome -- 4.2. Collagen synthesis -- 4.3. Collagen post-translational modification, folding and secretion -- 4.4. ECM remodeling -- 4.5. Ectopic calcification -- 4.6. mTOR signaling -- 4.7. TGFβ signaling -- 5. Chronotherapy for tendinopathy treatment -- 5.1. Aging of tendon clock -- 5.2. Possible methods of tendon clock entrainment -- 5.3. Implications for around-the-clock tendon care -- 6. Conclusions and implications -- Acknowledgments -- References -- Chapter Twelve: Mechanistic insights into skeletal development gained from genetic disorders -- 1. Introduction -- 2. Genetic control of patterning the appendicular skeleton -- 3. Skeletal morphogenesis: Integrated control of chondrocyte differentiation -- 4. Integrated signaling control of osteoblast differentiation and activity -- 5. Ciliopathies and the primary cilia in skeletal development -- 6. Planar cell polarity in the development of growth plate -- 7. The impact of ER stress signaling on chondrocyte differentiation -- 8. Non-coding mutations and regulatory control of skeletal development -- 9. Impacting 3D genome folding in skeletal disorders. , 10. Mechanistic insights from skeletal disorders: Impacting the path to therapy.