Neural induction and patterning (L9) Flashcards
How does the organiser induce neural and mesodermal tissues?
Under the influence of genes like siamois and Gsc, the organiser intrinsically expressed unique secreted products that are all antagonists of either BMP or components of its signalling pathway.
What effect do BMP antagonists have?
BMP antagonists act by preventing interaction of ligand and receptor. Their effect on ectoderm cells that lie adjacent results in the ectoderm cells changing their fate. They are induced to a neural identity (neuralation)
ALl ectodermal cells secrete BMP which diffuses out of the cell and tends to act locally by binding to the BMP receptor (TGFbetaR) on adjacent cells and triggering the BMP signalling pathway. As long as this pathway is active, the cell will differentiate into epidermal ectoderm (skin) - BMP antagonists from the organiser stop this.
Give some examples of BMP antagonists and how they exert their action.
Chordin, noggin and follistatin. They diffuse into the same extracellular spaces as BMP and compete for TGFBr - so BMPs are no longer able to activate their receptor. If the cells don’t have this pathway, they will develop into neural ectoderm.
How do BMP antagonists also pattern mesoderm?
BMP antagonists act on non-organiser mesoderm to refine mesodermal fates.
1. Low levels if nodal give ventral mesoderm (the organiser is located dorsally).
2. High levels of nodal give the organiser.
Signals (chordin and noggin) act to inhibit BMPs to dorsalise and pattern the ventral mesoderm.
4. At the same time, antagonisms of BMPs in the ectoderm leads the tissue to acquire a neural identity.
As a result, you get neural tissue and different types of mesoderm. the BMP antagonists diffuse through the mesoderm and divide it into different regions. The blood and kidneys will arise from the ventral-most mesoderm and the heart and somites from the intermediate bit. The notochord is derived from the dorsal most mesoderm (essentially the organiser)
How was neural induction proven?
Via organiser grafts. In the 1920s, the organiser graft experiment was done by Spemann and Mongold. They grafted an organiser bit of induced mesoderm that lies directly above the Nieuwkoop centre from a donor to a host newt, and they found that a twinned embryo developed - with a complete secondary neural axis. The secondary axin was host-derived - showing that the organiser INDUCES tissue, rather than the neural tissue originates directly from it.
When does the AP axis become apparent and how?
The AP axis becomes apparent as the organiser autonomously differentiated and undergoes convergent extension. There are 3 main cell type precursors that form in the organiser region. These will form the anterior endoderm, prechordal mesoderm and notochord. Collectively these tissues are called the axial mesoderm. All undergo convergent extension so that the organiser cells try to coalesce and so end up forming a rod. This rod migrates inside the cells of the animal hemisphere, on top of the blastocoel, following a fibronectin-rich pathway that binds integrins expressed as a consequence of the cells becoming organiser cells (the cells in this region get turned into neural plate cells). They are both quite short but very important. They migrate up along the extending pathway extending forwards and they now mark the future anterior part of the embryo.
What are the last cells to migrate during the AP axis formation?
The last cells to migrate in are the long notochord cells - they will underlie most of the body and are the back of the notochord - they form the posterior end. The rest of the body is built around notochord cells.
What is gastrulation?
(the process of the convergent extension and forming of the rod of mesoderm that the rest of the body will form around)
Why is the organiser credited with making both AP and DV axes?
After gastrulation, the axial mesoderm now lies under prospective neural tissue (a dorsal structure) which is why the organiser is initially referred to as marking the future dorsal axis, as well as the AP axis.
Why is the axial mesoderm important?
Development of the axial mesoderm (anterior endoderm/prechordal mesoderm/notochord) drives elongation and transition from the neural plate to the neural tube.
Explain the formation of the neural tube and how it is an example of the activation-transformation model.
The neural plate grows and elongates along the AP axis, and then rolls into the neural tube. Signals from the notochord cause cells and the back end if the neural plate to proliferate. At the same time, other signals from the notochord transform these cells from an anterior identity to a posterior identity. I.e they turn off transcription factors that dictate anterior identity and turn off transcription factors that dictate posterior identity. This is an example of the activation-transformation model (the cells are activated and they then transform into something else). This model is the basis for the formation of forebrain and hindbrain differentiation.
Explain the different antagonists used to establish the early AP axis.
Establishing an early AP axis means BMP and WNt antagonists are maintained anteriorly. FGFs , Wnt and retinoic acid are expressed posteriorly and promote growth of the neural plate, and posterior cell fates. A core concept in development is establishing a regional pattern by placing 2 antagonistic molecules at each end of a forming structure.
How does establishing the axis allow for patterning?
Different regions of the axis have different amounts of morphogens and signalling molecules. As a result, different regions of the neuroaxis come to express different Hox genes. the net effect/importance of these is especially well understood in the rhombomeres of the hindbrain E.g. particular nerves derived from discrete rhombomeres. An interaction between hindbrain and forebrain cells induces midbrain cells at the boundary.
How is the neural tissue patterned along the DV axis?
After the single-cell-thick neural plate (aka the neuroepithelium) is induced, it rolls up into the neural tube. The lateral edges fuse to become the dorsal part of the neural tube. It pinches off from the overlying ectoderm. This transforms the mediolateral axis into the dorsoventral one. This happens as the mesoderm elongates and becomes the notochord. So you end up with a neural tube, that has the notochord ventrally. The cells that were on the lateral edge delaminate and become neural crest cells as the tube pinches off.
What is the significance of roof plate cells?
The roof plate cells (at the top of the neural plate) begin to themselves upregulate BMPs and WNts. They’re secreted and diffuse into the dorsal neural tube. They induce the expression of a set of transcription factors (Pax6/7/3 and Lim1) that cause neural tube progenitors to acquire dorsal fates. Until recently it was thought that BMPs coming from the roof plate act as morphogens to induce different types of dorsal cells. But recent work suggests that the roof plate expresses many different BMPs, each of which induces a particular dorsal cell type. BMPs that derive from the surface ectoderm (above the dorsal neural tube) initially induce their own expression in the immediately adjacent dorsal spinal cord - in a wedge of neural plate border cells that are retained (roof plate cells) - signals from here and the surface ectoderm then act as local morphogens to pattern other parts of the dorsal spinal cord (e.g.neural crest cells and dorsal sensory relay interneurons)
