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Current Topics in Developmental Biology 2019Development of the axial skeleton is a complex, stepwise process that relies on intricate signaling and coordinated cellular differentiation. Disruptions to this process... (Review)
Review
Development of the axial skeleton is a complex, stepwise process that relies on intricate signaling and coordinated cellular differentiation. Disruptions to this process can result in a myriad of skeletal malformations that range in severity. The notochord and the sclerotome are embryonic tissues that give rise to the major components of the intervertebral discs and the vertebral bodies of the spinal column. Through a number of mouse models and characterization of congenital abnormalities in human patients, various growth factors, transcription factors, and other signaling proteins have been demonstrated to have critical roles in the development of the axial skeleton. Balance between opposing growth factors as well as other environmental cues allows for cell fate specification and divergence of tissue types during development. Furthermore, characterization of progenitor cells for specific cell lineages has furthered the understanding of specific spatiotemporal cues that cells need in order to initiate and complete development of distinct tissues. Identifying specific marker genes that can distinguish between the various embryonic and mature cell types is also of importance. Clinically, understanding developmental clues can aid in the generation of therapeutics for musculoskeletal disease through the process of developmental engineering. Studies into potential stem cell therapies are based on knowledge of the normal processes that occur in the embryo, which can then be applied to stepwise tissue engineering strategies.
Topics: Animals; Bone and Bones; Humans; Intervertebral Disc; Nucleus Pulposus; Signal Transduction; Somites
PubMed: 30902259
DOI: 10.1016/bs.ctdb.2018.11.018 -
BMC Developmental Biology May 2009The polarization of somite-derived sclerotomes into anterior and posterior halves underlies vertebral morphogenesis and spinal nerve segmentation. To characterize the...
BACKGROUND
The polarization of somite-derived sclerotomes into anterior and posterior halves underlies vertebral morphogenesis and spinal nerve segmentation. To characterize the full extent of molecular differences that underlie this polarity, we have undertaken a systematic comparison of gene expression between the two sclerotome halves in the mouse embryo.
RESULTS
Several hundred genes are differentially-expressed between the two sclerotome halves, showing that a marked degree of molecular heterogeneity underpins the development of somite polarity.
CONCLUSION
We have identified a set of genes that warrant further investigation as regulators of somite polarity and vertebral morphogenesis, as well as repellents of spinal axon growth. Moreover the results indicate that, unlike the posterior half-sclerotome, the central region of the anterior-half-sclerotome does not contribute bone and cartilage to the vertebral column, being associated instead with the development of the segmented spinal nerves.
Topics: Animals; Body Patterning; Cell Differentiation; Embryo, Mammalian; Gene Expression Regulation, Developmental; In Situ Hybridization; Mice; Neurogenesis; RNA; Somites; Spinal Nerves
PubMed: 19463158
DOI: 10.1186/1471-213X-9-30 -
Physiology (Bethesda, Md.) Mar 2023The significance of the coupling delay, which is the time required for interactions between coupled oscillators, in various oscillatory dynamics has been investigated... (Review)
Review
The significance of the coupling delay, which is the time required for interactions between coupled oscillators, in various oscillatory dynamics has been investigated mathematically for more than three decades, but its biological significance has been revealed only recently. In the segmentation clock, which regulates the periodic formation of somites in embryos, Hes7 expression oscillates synchronously between neighboring presomitic mesoderm (PSM) cells, and this synchronized oscillation is controlled by Notch signaling-mediated coupling between PSM cells. Recent studies have shown that inappropriate coupling delays dampen and desynchronize Hes7 oscillations, as simulated mathematically, leading to the severe fusion of somites and somite-derived tissues such as the vertebrae and ribs. These results indicate the biological significance of the coupling delay in synchronized Hes7 oscillations in the segmentation clock. The recent development of an in vitro PSM-like system will facilitate the detailed analysis of the coupling delay in synchronized oscillations.
Topics: Humans; Basic Helix-Loop-Helix Transcription Factors; Somites; Signal Transduction
PubMed: 36256636
DOI: 10.1152/physiol.00023.2022 -
Developmental Biology Jan 2004Vertebrate segmentation is manifested during embryonic development as serially repeated units termed somites that give rise to vertebrae, ribs, skeletal muscle and... (Review)
Review
Vertebrate segmentation is manifested during embryonic development as serially repeated units termed somites that give rise to vertebrae, ribs, skeletal muscle and dermis. Many theoretical models including the "clock and wavefront" model have been proposed. There is compelling genetic evidence showing that Notch-Delta signaling is indispensable for somitogenesis. Notch receptor and its target genes, Hairy/E(spl) homologues, are known to be crucial for the ticking of the segmentation clock. Through the work done in mouse, chick, Xenopus and zebrafish, an oscillator operated by cyclical transcriptional activation and delayed negative feedback regulation is emerging as the fundamental mechanism underlying the segmentation clock. Ubiquitin-dependent protein degradation and probably other posttranslational regulations are also required. Fgf8 and Wnt3a gradients are important in positioning somite boundaries and, probably, in coordinating tail growth and segmentation. The circadian clock is another biochemical oscillator, which, similar to the segmentation clock, is operated with a negative transcription-regulated feedback mechanism. While the circadian clock uses a more complicated network of pathways to achieve homeostasis, it appears that the segmentation clock exploits the Notch pathway to achieve both signal generation and synchronization. We also discuss mathematical modeling and future directions in the end.
Topics: Animals; Biological Evolution; Circadian Rhythm; Cleavage Stage, Ovum; Gene Expression Regulation, Developmental; Membrane Proteins; Models, Biological; Models, Theoretical; Morphogenesis; Receptors, Notch; Signal Transduction; Somites; Vertebrates
PubMed: 14697349
DOI: 10.1016/j.ydbio.2003.07.003 -
Developmental Biology May 2006Somitogenesis, the sequential formation of a periodic pattern along the antero-posterior axis of vertebrate embryos, is one of the most obvious examples of the segmental... (Review)
Review
Somitogenesis, the sequential formation of a periodic pattern along the antero-posterior axis of vertebrate embryos, is one of the most obvious examples of the segmental patterning processes that take place during embryogenesis and also one of the major unresolved events in developmental biology. In this article, we develop a mathematical formulation of a new version of the Clock and Wavefront model proposed by Pourquié and co-workers (Dubrulle, J., McGrew, M.J., Pourquié, O., 2001. FGF signalling controls somite boundary position and regulates segmentation clock control of spatiotemporal Hox gene activation. Cell 106, 219-232). Dynamic expression of FGF8 in the presomitic mesoderm constitutes the wavefront of determination which sweeps along the body axis interacting as it moves with the segmentation clock to gate cells into somites. We also show that the model can mimic the anomalies formed when progression of the wavefront is disturbed and make some experimental predictions that can be used to test the hypotheses underlying the model.
Topics: Animals; Biological Clocks; Body Patterning; Humans; Models, Biological; Somites
PubMed: 16546158
DOI: 10.1016/j.ydbio.2006.01.018 -
The International Journal of... 2009In vertebrates, the paraxial mesoderm differentiates into several structures, including the axial skeleton. The genetic mechanisms that control positional information in... (Review)
Review
In vertebrates, the paraxial mesoderm differentiates into several structures, including the axial skeleton. The genetic mechanisms that control positional information in the paraxial mesoderm along the anterior-posterior axis are responsible for the development of a skeleton with the appropriate vertebral formula, i.e. a specific number of cervical, thoracic, lumbar, sacral and caudal vertebrae. These control mechanisms are complex and involve molecules of different kinds, including transcription factors, like those encoded by the Hox genes, and signalling molecules, like those involved in Gdf11, FGF, retinoic acid or WNT signalling. Recent experiments indicate that most of the positional information for the paraxial mesoderm is encoded during the initial steps of its development in the presomitic mesoderm, although it is only decoded later during differentiation of the somites. The genesis of positional identity may be linked to the process of somitogenesis, which also occurs in the presomitic mesoderm as a result of complex interactions involving oscillatory activity of components of the Notch and WNT signalling pathways and antagonistic gradients of FGF/WNT and retinoic acid. The possible connections between Hox genes and all these signalling processes to generate a properly patterned axial skeleton are discussed in this review.
Topics: Animals; Body Patterning; Gene Expression Regulation, Developmental; Homeodomain Proteins; Mesoderm; Signal Transduction; Somites; Spine; Vertebrates
PubMed: 19247958
DOI: 10.1387/ijdb.072276mm -
Development (Cambridge, England) Jun 2017During vertebrate somitogenesis, retinoic acid is known to establish the position of the determination wavefront, controlling where new somites are permitted to form...
During vertebrate somitogenesis, retinoic acid is known to establish the position of the determination wavefront, controlling where new somites are permitted to form along the anteroposterior body axis. Less is understood about how RAR regulates somite patterning, rostral-caudal boundary setting, specialization of myotome subdivisions or the specific RAR subtype that is required for somite patterning. Characterizing the function of RARβ has been challenging due to the absence of embryonic phenotypes in murine loss-of-function studies. Using the system, we show that RARβ2 plays a specific role in somite number and size, restriction of the presomitic mesoderm anterior border, somite chevron morphology and hypaxial myoblast migration. is the RAR subtype whose expression is most upregulated in response to ligand and its localization in the trunk somites positions it at the right time and place to respond to embryonic retinoid levels during somitogenesis. RARβ2 positively regulates a marker of hypaxial muscle, and negatively regulates via to restrict the anterior boundaries of the presomitic mesoderm and caudal progenitor pool. These results demonstrate for the first time an early and essential role for RARβ2 in vertebrate somitogenesis.
Topics: Animals; Benzoates; Biomarkers; Embryo, Nonmammalian; Embryonic Development; Gene Expression Regulation, Developmental; Larva; Mesoderm; Models, Biological; Morpholinos; Muscles; Promoter Regions, Genetic; Protein Isoforms; Receptors, Retinoic Acid; Retinoic Acid Receptor alpha; Retinoids; Somites; Tretinoin; Xenopus Proteins; Xenopus laevis; Retinoic Acid Receptor gamma
PubMed: 28432217
DOI: 10.1242/dev.144345 -
Journal of Anatomy Oct 2019Somites are epithelial segments of the paraxial mesoderm. Shortly after their formation, the epithelial somites undergo extensive cellular rearrangements and form...
Somites are epithelial segments of the paraxial mesoderm. Shortly after their formation, the epithelial somites undergo extensive cellular rearrangements and form specific somite compartments, including the sclerotome and the myotome, which give rise to the axial skeleton and to striated musculature, respectively. The dynamics of somite development varies along the body axis, but most research has focused on somite development at thoracolumbar levels. The development of tail somites has not yet been thoroughly characterized, even though vertebrate tail development has been intensely studied recently with respect to the termination of segmentation and the limitation of body length in evolution. Here, we provide a detailed description of the somites in the avian tail from the beginning of tail formation at HH-stage 20 to the onset of degeneration of tail segments at HH-stage 27. We characterize the formation of somite compartment formation in the tail region with respect to morphology and the expression patterns of the sclerotomal marker gene paired-box gene 1 (Pax1) and the myotomal marker genes MyoD and myogenic factor 5 (Myf5). Our study gives insight into the development of the very last segments formed in the avian embryo, and provides a basis for further research on the development of tail somite derivatives such as tail vertebrae, pygostyle and tail musculature.
Topics: Animals; Birds; Chick Embryo; Embryonic Development; Somites; Tail
PubMed: 31225912
DOI: 10.1111/joa.13032 -
Developmental Biology Jan 2017Somitogenesis and subsequent axial skeletal development is regulated by the interaction of pathways that determine the periodicity of somite formation, rostrocaudal...
Somitogenesis and subsequent axial skeletal development is regulated by the interaction of pathways that determine the periodicity of somite formation, rostrocaudal somite polarity and segment identity. Here we use a hypomorphic mutant mouse line to demonstrate that Supt20 (Suppressor of Ty20) is required for development of the axial skeleton. Supt20 hypomorphs display fusions of the ribs and vertebrae at lower thoracic levels along with anterior homeotic transformation of L1 to T14. These defects are preceded by reduction of the rostral somite and posterior shifts in Hox gene expression. While cycling of Notch target genes in the posterior presomitic mesoderm (PSM) appeared normal, expression of Lfng was reduced. In the anterior PSM, Mesp2 expression levels and cycling were unaffected; yet, expression of downstream targets such as Lfng, Ripply2, Mesp1 and Dll3 in the prospective rostral somite was reduced accompanied by expansion of caudal somite markers such as EphrinB2 and Hes7. Supt20 interacts with the Gcn5-containing SAGA histone acetylation complex. Gcn5 hypomorphic mutant embryos show similar defects in axial skeletal development preceded by posterior shift of Hoxc8 and Hoxc9 gene expression. We demonstrate that Gcn5 and Supt20 hypomorphs show similar defects in rostral-caudal somite patterning potentially suggesting shared mechanisms.
Topics: Animals; Body Patterning; Bone Development; Cell Movement; Cell Polarity; Gene Expression Regulation, Developmental; Mesoderm; Mice; Mutation; Neural Crest; Phenotype; Receptors, Notch; Signal Transduction; Somites; Spine; Transcription Factors
PubMed: 27894818
DOI: 10.1016/j.ydbio.2016.11.009 -
The International Journal of... 2018The chick embryo has provided a prominent model system for the study of segmental patterning in the nervous system. During early development, motor and sensory axon... (Review)
Review
The chick embryo has provided a prominent model system for the study of segmental patterning in the nervous system. During early development, motor and sensory axon growth cones traverse the anterior/rostral half of each somite, so avoiding the developing vertebral components and ensuring separation of spinal nerves from vertebral bones. A glycoprotein expressed on the surface of posterior half-somite cells confines growth cones to the anterior half-somites by a contact repulsive mechanism. Hindbrain segmentation is also a conspicuous feature of chick brain development. We review how its contemporary analysis was initiated in the chick embryo, and the advantages the chick system continues to provide in its detailed elucidation at both molecular and neural circuit levels.
Topics: Animals; Axons; Chick Embryo; Chickens; Embryology; Glycoproteins; History, 19th Century; History, 20th Century; History, 21st Century; Humans; Lectins; Peripheral Nervous System; Rhombencephalon; Somites
PubMed: 29616726
DOI: 10.1387/ijdb.170297rk