Colle, Charlotte Christiane; (2022) Exploring the molecular mechanisms of competence for neural induction. Doctoral thesis (Ph.D), UCL (University College London).

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Abstract

During embryonic development, groups of cells become assigned to different fates (to form different tissues and organs) in response to signals from a small set of specialised signalling regions, called “organisers”. However, the responsiveness of particular groups of cells to these signals is limited in both time and in space: the ability of a tissue to respond is called “competence”. Although this concept was proposed a long time ago (around 1933, by Waddington) there has been no information on the underlying reasons for why some cells are competent to respond to inducing signals and others are not. Here we investigated this systematically for the case of “neural induction” (how an organiser generates the central nervous system from responding cells), using a series of sophisticated molecular tools in combination with embryological manipulations on chick embryos. Comparing four different groups of cells (one competent and three different non-competent ones), we discovered that although all three non-competent tissues fail to generate a proper nervous system, as expected, all three still hold individual responses along the neural induction cascade. Interestingly, we found that all three non-competent epiblast regions exhibit higher level of BMP activity in comparison to the competent epiblast. BMP inhibition, required for neural induction in the competent epiblast, could not be achieved by a node in any of these three non-competent epiblast regions. In addition, we found lower FGF receptors availability in non-competent regions in comparison to the competent population. Surprisingly, we showed that FGF, but not a node could fully repress BMP activity in non-competent epiblast, suggesting that despite a lack FGF receptors, these epiblast regions still respond to FGF. Together these findings provide the first insights into the molecular mechanisms that are required to ensure that the ability to respond to inducing signals are restricted appropriately to the right cells at the right time.

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