Vertebrate Skeletal Development

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