Somitogenesis: Difference between revisions
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* '''From dynamic expression patterns to boundary formation in the presomitic mesoderm'''<ref><pubmed>22761566</pubmed></ref> "The segmentation of the vertebrate body is laid down during early embryogenesis. The formation of signaling gradients, the periodic expression of genes of the Notch-, Fgf- and Wnt-pathways and their interplay in the unsegmented presomitic mesoderm (PSM) precedes the rhythmic budding of nascent somites at its anterior end, which later develops into epithelialized structures, the somites. Although many in silico models describing partial aspects of somitogenesis already exist, simulations of a complete causal chain from gene expression in the growth zone via the interaction of multiple cells to segmentation are rare. Here, we present an enhanced gene regulatory network (GRN) for mice in a simulation program that models the growing PSM by many virtual cells and integrates WNT3A and FGF8 gradient formation, periodic gene expression and Delta/Notch signaling. Assuming Hes7 as core of the somitogenesis clock and LFNG as modulator, we postulate a negative feedback of HES7 on Dll1 leading to an oscillating Dll1 expression as seen in vivo. Furthermore, we are able to simulate the experimentally observed wave of activated NOTCH (NICD) as a result of the interactions in the GRN. We esteem our model as robust for a wide range of parameter values with the Hes7 mRNA and protein decays exerting a strong influence on the core oscillator. Moreover, our model predicts interference between Hes1 and HES7 oscillators when their intrinsic frequencies differ. In conclusion, we have built a comprehensive model of somitogenesis with HES7 as core oscillator that is able to reproduce many experimentally observed data in mice." | * '''From dynamic expression patterns to boundary formation in the presomitic mesoderm'''<ref><pubmed>22761566</pubmed>| [http://www.ploscompbiol.org/article/info%3Adoi%2F10.1371%2Fjournal.pcbi.1002586 PLoS Comput Biol.]</ref> "The segmentation of the vertebrate body is laid down during early embryogenesis. The formation of signaling gradients, the periodic expression of genes of the Notch-, Fgf- and Wnt-pathways and their interplay in the unsegmented presomitic mesoderm (PSM) precedes the rhythmic budding of nascent somites at its anterior end, which later develops into epithelialized structures, the somites. Although many in silico models describing partial aspects of somitogenesis already exist, simulations of a complete causal chain from gene expression in the growth zone via the interaction of multiple cells to segmentation are rare. Here, we present an enhanced gene regulatory network (GRN) for mice in a simulation program that models the growing PSM by many virtual cells and integrates WNT3A and FGF8 gradient formation, periodic gene expression and Delta/Notch signaling. Assuming Hes7 as core of the somitogenesis clock and LFNG as modulator, we postulate a negative feedback of HES7 on Dll1 leading to an oscillating Dll1 expression as seen in vivo. Furthermore, we are able to simulate the experimentally observed wave of activated NOTCH (NICD) as a result of the interactions in the GRN. We esteem our model as robust for a wide range of parameter values with the Hes7 mRNA and protein decays exerting a strong influence on the core oscillator. Moreover, our model predicts interference between Hes1 and HES7 oscillators when their intrinsic frequencies differ. In conclusion, we have built a comprehensive model of somitogenesis with HES7 as core oscillator that is able to reproduce many experimentally observed data in mice." | ||
* '''FGF4 and FGF8 comprise the wavefront activity that controls somitogenesis'''<ref><pubmed>21368122</pubmed></ref> "Somites form along the embryonic axis by sequential segmentation from the presomitic mesoderm (PSM) and differentiate into the segmented vertebral column as well as other unsegmented tissues. Somites are thought to form via the intersection of two activities known as the clock and the wavefront. Previous work has suggested that fibroblast growth factor (FGF) activity may be the wavefront signal, which maintains the PSM in an undifferentiated state. However, it is unclear which (if any) of the FGFs expressed in the PSM comprise this activity, as removal of any one gene is insufficient to disrupt early somitogenesis. Here we show that when both Fgf4 and Fgf8 are deleted in the PSM, expression of most PSM genes is absent, including cycling genes, WNT pathway genes, and markers of undifferentiated PSM. Significantly, markers of nascent somite cell fate expand throughout the PSM, demonstrating the premature differentiation of this entire tissue, a highly unusual phenotype indicative of the loss of wavefront activity. When WNT signaling is restored in mutants, PSM progenitor markers are partially restored but premature differentiation of the PSM still occurs, demonstrating that FGF signaling operates independently of WNT signaling. This study provides genetic evidence that FGFs are the wavefront signal and identifies the specific FGF ligands that encode this activity. Furthermore, these data show that FGF action maintains WNT signaling, and that both signaling pathways are required in parallel to maintain PSM progenitor tissue." | * '''FGF4 and FGF8 comprise the wavefront activity that controls somitogenesis'''<ref><pubmed>21368122</pubmed></ref> "Somites form along the embryonic axis by sequential segmentation from the presomitic mesoderm (PSM) and differentiate into the segmented vertebral column as well as other unsegmented tissues. Somites are thought to form via the intersection of two activities known as the clock and the wavefront. Previous work has suggested that fibroblast growth factor (FGF) activity may be the wavefront signal, which maintains the PSM in an undifferentiated state. However, it is unclear which (if any) of the FGFs expressed in the PSM comprise this activity, as removal of any one gene is insufficient to disrupt early somitogenesis. Here we show that when both Fgf4 and Fgf8 are deleted in the PSM, expression of most PSM genes is absent, including cycling genes, WNT pathway genes, and markers of undifferentiated PSM. Significantly, markers of nascent somite cell fate expand throughout the PSM, demonstrating the premature differentiation of this entire tissue, a highly unusual phenotype indicative of the loss of wavefront activity. When WNT signaling is restored in mutants, PSM progenitor markers are partially restored but premature differentiation of the PSM still occurs, demonstrating that FGF signaling operates independently of WNT signaling. This study provides genetic evidence that FGFs are the wavefront signal and identifies the specific FGF ligands that encode this activity. Furthermore, these data show that FGF action maintains WNT signaling, and that both signaling pathways are required in parallel to maintain PSM progenitor tissue." |
Revision as of 15:59, 9 August 2012
Introduction
The term used to describe the process of segmentation of the paraxial mesoderm within the trilaminar embryo body to form pairs of somites, or balls of mesoderm. In humans, the first somite pair appears at day 20 and adds caudally at 1 somite pair/90 minutes until on average 44 pairs eventually form.
A somite is added either side of the notochord (axial mesoderm) to form a somite pair. The segmentation does not occur in the head region, and begins cranially (head end) and extends caudally (tailward) adding a somite pair at regular time intervals. The process is sequential and therefore used to stage the age of many different species embryos based upon the number visible somite pairs.
Some Recent Findings
|
Recent References | References
Presomitic Mesoderm
- Within the mesodermal layer either side of the notochord (axial mesoderm) lie the paraxial mesoderm strips.
- Below the unsegmented cranial paraxial mesoderm region the region that will later segment is described as presomitic mesoderm (PSM).
- This PSM is being "patterned" by two two molecular activities described as the "clock" and the "wavefront" (reviewed[3])
- Many different molecular factors are involved in this patterning effect.
- Hes7, FGF, Sprouty4, Notch, Shh
- notochord influences somite formation, notochord removal increases the period of molecular clock oscillations.[4]
Human Embryo - First Somites
Human embryo first somite pairs (week 4, Carnegie stage 9)
Mesoderm to Somite
Mesoderm means the "middle layer" and it is from this layer that nearly all the bodies connective tissues are derived. In early mesoderm development a number of transient structures will form and then be lost as tissue structure is patterned and organised. Humans are vertebrates, with a "backbone", and the first mesoderm structure we will see form after the notochord will be somites.
- During segmentation the outer cell layer forms an epithelial layer over a still mesenchymal organization of cells at the core.
- The early forming somite has a cavity at its core called a "somitocoel" that later fills with proliferating mesoderm cells.
Somite to Sclerotome and Dermomyotome
Somite initially forms 2 main regional components
- ventromedial region - sclerotome forms vertebral body and intervertebral disc
- dorsolateral region - dermomyotome forms dermis and skeletal muscle
Sclerotome
- The left and right sclerotomes from the same segmental level engulf the notochord.
- Each segmental level is then resegmented in a rostrocaudal direction.
Dermomyotome
- The dermomyotome is divided into a dorsal and ventral half.
- Dorsal - dermatome.
- Ventral - myotome, this will also divide into a dorsal and ventral half that contribute the epaxial and hypaxial skeletal muscle groups respectively.
Additional Images
References
- ↑ <pubmed>22761566</pubmed>| PLoS Comput Biol.
- ↑ <pubmed>21368122</pubmed>
- ↑ <pubmed>17024300</pubmed>
- ↑ <pubmed>20615943</pubmed>
Reviews
<pubmed>18482400</pubmed> <pubmed>21038776</pubmed> <pubmed>21038775</pubmed> <pubmed>17988868</pubmed> <pubmed>17643270</pubmed> <pubmed>17600784</pubmed> <pubmed>17024300</pubmed> <pubmed>15964269</pubmed> <pubmed>15309628</pubmed> <pubmed>15338303</pubmed>
Articles
<pubmed>12649586</pubmed>| Cells Tissues Organs
Search PubMed
Search NLM Online Textbooks: "Somitogenesis" : Developmental Biology | The Cell- A molecular Approach | Molecular Biology of the Cell | Endocrinology
Search Pubmed: Somitogenesis | Formation | Sclerotome | Hes7
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Cite this page: Hill, M.A. (2024, March 28) Embryology Somitogenesis. Retrieved from https://embryology.med.unsw.edu.au/embryology/index.php/Somitogenesis
- © Dr Mark Hill 2024, UNSW Embryology ISBN: 978 0 7334 2609 4 - UNSW CRICOS Provider Code No. 00098G