eprintid: 10142768 rev_number: 12 eprint_status: archive userid: 699 dir: disk0/10/14/27/68 datestamp: 2022-03-17 13:02:04 lastmod: 2022-09-01 06:11:19 status_changed: 2022-03-17 13:02:04 type: thesis metadata_visibility: show sword_depositor: 699 creators_name: Colle, Charlotte Christiane title: Exploring the molecular mechanisms of competence for neural induction ispublished: unpub divisions: C08 divisions: D09 divisions: B02 divisions: UCL note: Copyright © The Author 2022. Original content in this thesis is licensed under the terms of the Creative Commons Attribution-NonCommercial 4.0 International (CC BY-NC 4.0) Licence (https://creativecommons.org/licenses/by-nc/4.0/). Any third-party copyright material present remains the property of its respective owner(s) and is licensed under its existing terms. Access may initially be restricted at the author’s request. 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. date: 2022-02-28 date_type: published oa_status: green full_text_type: other thesis_class: doctoral_embargoed thesis_award: Ph.D language: eng primo: open primo_central: open_green verified: verified_manual elements_id: 1937320 lyricists_name: Colle, Charlotte lyricists_id: CCHAR00 actors_name: Colle, Charlotte actors_id: CCHAR00 actors_role: owner full_text_status: public pagerange: 1-217 pages: 217 institution: UCL (University College London) department: Cell and Developmental Biology thesis_type: Doctoral citation: Colle, Charlotte Christiane; (2022) Exploring the molecular mechanisms of competence for neural induction. Doctoral thesis (Ph.D), UCL (University College London). Green open access document_url: https://discovery-pp.ucl.ac.uk/id/eprint/10142768/1/Corrected_Thesis_COLLE.pdf