Cell segregation in gastrulation: the role of cell fate specification

点击翻译按钮获取中文摘要

The development of multicellular organisms is driven by the intimately connected activities of patterning and morphogenesis. While patterning denotes the generation and organization of cell fates in space and time, morphogenesis encompasses the processes by which the organism takes shape. Morphogenesis of multicellular organisms typically involves organized changes in the number, size, shape and position of their constituent cells. There is mounting evidence that cell fate specification determines the morphogenetic potential of cells, and conversely, that cell morphogenesis influences cell fate specification and maintenance1. However, the dynamic interplay between cell fate specification and morphogenesis within a developing organism has only begun to be elucidated. The first major morphogenetic process in the development of most multicellular organisms is gastrulation. In gastrulation, progenitor cells segregate into distinct population of cells that give rise to the different germ layers ¿ ectoderm, mesoderm and endoderm2. The formation and spatial organization of germ layers have been most extensively studied in amphibian embryos and involve a complex interplay between cell migration and intercalation3. Seminal studies by Townes and Holtfreter from the middle of the last century have demonstrated that primary germ layer progenitor cells taken into single cell suspensions have the remarkable capacity to self-organize into distinct germ layers, the relative position of which resembles their embryonic origin4. This self-organizing capacity of germ layer progenitor cells has been explained by differences in their adhesive properties5, although the specific contribution of differential cell adhesion, as opposed to other cell properties such as cell cortex tension and cell migration, to germ layer formation during gastrulation remains unclear6. Moreover, while models that explain progenitor cell segregation and germ layer formation by differential cell adhesion and/or cortex tension commonly assume that each progenitor cell type displays invariant and uniform properties determining its specific morphogenetic potential7-9, observations made in vitro and in vivo suggest that progenitor cells undergo highly dynamic changes in cell fate specification and differentiation during germ layer formation10-12. In this interdisciplinary research proposal, we will determine the relationship between progenitor cell fate specification ¿ the reversible process by which blastoderm cells become capable of differentiating into ectoderm, mesoderm and endoderm cells ¿ and progenitor cell-cell contact formation in driving germ layer formation during gastrulation. We will determine how progenitor cell fate specification and cell-cell contact formation influence each other during gastrulation, and how their interaction influences progenitor cell segregation and tissue organization. To this end, we will follow a reductionist approach and first use minimal in vitro cel