S3: Musculoskeletal Development I - Somites and Bones Flashcards
What order are somites formed?
From somite 1 and counting upwards. The first somites are formed at the occipital/cervical level.
What is gastrulation?
Gastrulation is when you go from a two layer germ disc to a three layer embryo.
Describe how gastrulation generates the three primary germ layers
Cells move from either side into the midline of the neural plate and the epithelial cells become mesochymal by undergoing a epithelial-mesochymal transition.
The cells in the middle will ingress and differentiate to give rise to the endoderm, and ectoderm.
- The ectoderm is on the outside, mesoderm is in the middle and endoderm is on the inside.
What occurs at the same time as gastrulation?
The primitive streak is progressing across the embryonic disc, the ectoderm is forming neural tissue. It rolls up to from a neural tube to be eventually covered by the ectoderm.
Describe the different mesoderms and what they form
Notochord (initial mesodermal structure formed as the embryo is elongating) send out other signals that influence the somites.
Paraxial mesoderm is the mesoderm that forms the somites.
Intermediate mesoderm lies between lateral and paraxial mesoderm.
How do somites form the bulk of the body? What forms the rest?
Axial skeleton - somites which form vertebrae and ribs.
Axial muscle - somites which form vertebrae, throrax and abdomen.
Appendicular muscles - somites form flexors and extensors.
Appendicular skeleton - limb buds which forms the limbs, digits and girdles.
Describe somites and somitogenesis
- Somites are formed from proliferating presomitic mesoderm (PSM) and they are laid down sequentially from cranial to caudal.The most recently formed somite is the one next to the pre-somitic mesoderm.
- They are formed regularly with the time characteristic of the species.
- The total number of somites formed is also characteristic of the species e.g. human 44. They are independent to the variations in embryonic size.
- Cranial and caudal halves of each somite are different and contain different properties.
- Each somite has different fate encoded in PSM by Hox genes.
- Somites are initially paired epithelial spheres each side of the neural tube.
How is the regular formation of somites acheived?
It is achieved by a clock mechanism to mark time (group of cells) plus a wavefront or ‘trigger’ to form each somite at each set period. This is described using the ‘clock and wave front model’.
Describe the clock and wave front model and three tier model of the segmentation clock
- Oscillations of the clock are generated by delayed negative feedback on gene expression.
- The trigger is provided by a gradient threshold of signalling proteins.
There are three tiers in which cell behaviour is governed to make the periodic formation of somite:
- BOTTOM TIER: There is an individual clock (cell) that is counting time (individual clock within each cell governed by level of genes and protein the cell is expressing). Protein and mRNA instability and transcriptional and translational delay is sufficient to create cycling. The protein acts as a negative feedback loop on its own production by targeting its own gene. Over time, the protein and mRNA decays which allows the gene to turn back on. This is a simple homeostatic mechanism which will oscillate.
- MIDDLE TIER: Groups of cells that are local to one another are coupled together by group of receptors at their surface (notch receptors and delta ligands). Notch-Delta signals couple adjacent groups so they can coordinate their behaviour.
- UPPER TIER: A more global signal which are different triggers of somite formation and overall cells are told in particular points in the middle tier cycle to differentiate and become somites.
How do signalling molecules cause ‘wavefront’ formation?
Wavefront is formed by signalling molecules:
- Retinoic acid present at cranial end of embryo
- Fibroblast growth factor family and Wnt signalling family both at caudal end of embryo
The source of signal is the caudal end which is proliferating rapidly. The signal moves further and further away to the cranial end causing a ‘wavefront’ formation.
Describe somite diffrentiation
- The epithelial somite differentiates into two seperate layers: the dermomyotome and sclerotome.
- Dermomyotome further differentiates to dermatome and myotome.
- Syndetome forms at cranial and caudal boundary of each epithelial somite.
How is cartilage formed?
- Cartilage is formed through the process of chondrogenesis (chondrification).
- Chondrocytes secrete ECM (extracellular matrix) molecules such as aggrecan and collagen.
- Hyaline cartilage forms on the surface of most joints but isn’t ossified.
How is our skeleton initially formed?
Most of the skeleton is initially formed as cartilage skeleton before becoming mineralised to from bone. This is known as endochondral ossification.
How is our skeleton initially formed?
Most of the skeleton is initially formed as cartilage skeleton before becoming mineralised to from bone. This is known as endochondral ossification.
Describe the ossification of long bones (endochondral ossification)
- Chondrocytes generate a cartilage model.
- Chondrocytes condense towards the central region of long bones and they start to lay down matrix.
- They then undergo vascularisation and carry osteoblasts precursors to the condensed cartilage.
- Primary ossification centres start from the middle of the bone and spread out and are present by week 12.
- Mineralised bone replaces cartilage
- Ossification continues post-natally until about 20 years (hyperproliferation of chondrocytes is retained at the ends of long bones so they can continue to grow)
