The aim of this thesis is to further define the roles of a4 integrin and b1 integrin in the definitive haemopoietic system, more specifically in the initial stages of its establishment. We show that b1 integrin and a4 integrin are expressed on definitive haemopoietic stem cells from the embryonic day 11 aorta, gonads, mesenephorous region, day 13 foetal liver, day 13 peripheral blood and adult bone marrow, which represent the major developmental stages of the definitive haemopoietic system. In the day 13 foetal liver and adult bone marrow some a4 integrin negative definitive haemopopietic stem cells stem cells are also detected. Therefore, the expression of a4 integrin may be modulated as definitive haemopoietic stem cells mature in the later haemopoietic organs. By studying the generation of definitive haemopoietic stem cells in a4 integrin knockout embryos, a role for a4 integrin in the correct localisation and/or development of definitive haemopoietic stem cells in the foetal liver was revealed. In addition, these studies showed that the increasing defects observed in a4 integrin knockout mice are likely due to progressive defects in definitive haemopoietic stem cells as they develop in different haemopoietic microenvironments. Attempts to generate a reversible b1 integrin knockout which would enable identification of the time point at which b1 integrin is essential for definitive haemopoiesis is also discussed. In conclusion the data presented here supports previous studies on the role of b1 and a4 integrin in adult and embryonic definitive haemopoiesis and gives further information as to the time points at which these molecules are essential for the establishment of the definitive haemopoietic system and during its maintenance.
| Identifer | oai:union.ndltd.org:bl.uk/oai:ethos.bl.uk:652554 |
| Date | January 2000 |
| Creators | Hook, Lilian Alexandra |
| Publisher | University of Edinburgh |
| Source Sets | Ethos UK |
| Detected Language | English |
| Type | Electronic Thesis or Dissertation |
| Source | http://hdl.handle.net/1842/15048 |
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