| In the work that led to this Ph.D. thesis, I focused on two central questions in developmental biology: what does it mean to be an undifferentiated stem cell, and how does cell communication lead to pattern formation and differentiation. I used the mouse as organism of study for two main reasons: first, several types of stem cells can readily be isolated from mice; second, powerful tools are available in the mouse for genetic analyses of cell communication.; Part I of this thesis, which is comprised of Chapter 1, describes the transcriptional profiling of mouse embryonic, hematopoietic and neural stem cells using microarrays, as an approach to identifying genes and functions common to all stem cells.; Part II reports essential roles of the Hedgehog cell signaling pathway in mouse embryogenesis. Chapter 2 describes a requirement for Hedgehog signaling in establishment of the L/R axis, and in somite and heart development. Chapter 3 describes results showing that Hedgehog signaling is essential for proper anterior/posterior and radial patterning of the gut, and for epithelial stem cell proliferation and differentiation.; In Part III, which is comprised of Chapter 4, I propose a theoretical framework for stem cell biology based on the concepts of autopoiesis and complementarity. |
