Mesoderm segmentation (L10) Flashcards
Where does the mesoderm form?
At the primitive streak - the mesoderm precursors migrate inwards then spread out.
What are the different subdivisions of mesoderm? What does each become?
The mesoderm is subdivided into axial mesoderm (under the neural tube), paraxial mesoderm (next to the mesoderm), intermediate mesoderm and the lateral plate mesoderm.
The axial mesoderm becomes the notochord and prechordal mesoderm. Paraxial (somatic) mesoderm becomes the head and somites, which later develop into sclerotome (cartilage), syndotome (tendons), myotome (skeletal muscle), endothelium and dermatome (skin etc)
The intermediate mesoderm becomes the kidney and gonads. The lateral plate mesoderm becomes splanchnic (circulatory system), somatic (body cavity, pelvis, limb bones) and extraembryonic tissues
What are the properties of somites? Explain their evolutionary significance.
The paraxial mesoderm becomes segmented and forms somites (it doesn’t start off segmented). Somites are regular in size and show bilateral symmetry. They are the earliest evidence of segmentation in vertebrates. Mesoderm segmentation is conserved throughout evolution. It’s present in invertebrates as well as vertebrates. Segmentation varies in fish- different adaptations of somites allow for different swimming patterns. Somite number also dictates the number of vertebrae. Humans are born with 33 vertebrae, by adulthood they have 24, and 9 fused ones. A human embryo has 38-44 somites, while a chick has 55, mice have 65 and zebrafish have 33. The paraxial mesoderm forms in a continuous manner until the right number of somites has been reached. The timing of somite formation also remains constant throughout the species.
The pre-somatic mesoderm, although not segments, prefigures the future segmentation of somites. They form by budding off the pre-somatic mesoderm. In a chick, they form about every 90 mins.
Explain the clock and wavefront model.
Was proposed by Cooke and Zeeman in 1976. It explains how the periodicity of somite formation occurs. It proposes that a ‘clock’ ticks in the posterior pre-somatic mesoderm, and drives a ‘molecular oscillator’ that dictates the periodicity of somites ( 2 essential components). Where cells hit the travelling wave from, an abrupt change of property occurs leading to the decision to form somites. This can be in the oscillation of C-hairy (Hes/her in mouse/zebrafish) expression in the pre-somatic mesoderm (discovered by a PhD student). It shows a wave of expression with oscillations of about 90mins (which fits with the time it takes to make a somite in a chick)
Explain how Hair regulates the formation of the somites
Hair/Hes/her protein half-life and its function are critical for the oscillatory pattern of its mRNA. They are target genes of Notch signalling and are bHLH transcriptional repressors (the Hes-1 protein represses the Hes1 gene - the remaining protein is then degraded and no longer represses the gene - this is why it cycles). A number of clock genes belong to the Wnt, Notch and FGF signalling pathways. Presomatic mesoderm cells undergo 12 cycles of oscillations before forming somites, the cells don’t physically move but their expression changes. The position S_I marks the specification boundary of formation. When cells encounter the wavefront travelling in the opposite direction, the oscillations stop. The determination front is positioned at the interface of two opposing gradients. (RA and FGF8)
How do negative feedback regulations maintain the reverse relationship between RA and FGF8 gradients?
The FGF gradient moves away - FGF expression of RA- RA controls FGF8, they aren’t expressed in the same place, so their gradients are balanced. Raldh2 controls the synthesis of RA (activates it). Mesp2 is also activated by RA and inhibited by FGF8. Therefore, the expression of Mesp2 is restricted to the posterior, and ripply 2 is anterior.
How do boundaries between somites occur?
Boundary cells can induce boundary somite formation. Transplantation of a prospective somite boundary region into a non-boundary region can cause a new boundary.
Boundary cells instruct cells that are anterior to them to form a boundary. Notch family genes are expressed at the somite boundary and manipulating this notch drives boundary formation. The notch allows the production of lunatic fringe (lfng) which establishes the anterior boundary of the somite. Lunatic fringe = glycosyltransferase. Somite derivatives are affected in the absence of Notch signalling e.g. in a delta-like 3 mutant mouse - ossification centres so not align. In humans, a similar mutation can cause spondylocostal dysplasia (Jarcho Lewin syndrome)
What is the overall model for somite formation?
Molecular oscillator -> C-hairy-1 -> lunatic fringe -> delta1 (delta 1 doesn’t lead to somites so ignore) or notch 1 ->ephrins (cell adhesion molecules) -> cell adhesion changes -> somite formation - oscialltion slows down as the cell matures
What different notches are responsible for AP identity?
Acquisition of AP identity is Notch1 and D11 in pos and Notch2 and D13 in anterior.
