Gene expression during development: timing matters
During development, cell specification and differentiation requires the spatial and temporal coordination of gene expression. This is facilitated through accurate interaction between intercellular signalling and gene regulatory networks. Several regulatory motifs driving gene expression have been identified at the cellular level, and we are beginning to understand how morphogens determine the spatial regulation of cells in a tissue. However, little is known about the timing and coordination of gene expression in populations of cells. To address this, scientists from the EU-funded CELLCOORDINATION (Temporal coordination of gene expression during development) project set out to understand cell dynamics and coordination during differentiation and development over time. They employed embryonic stem (ES) cells to study in vitro, ES cell differentiation into mesendoderm (ME)/primitive streak (PS)-like cells. Live imaging of individual ES cells differentiated towards a PS-like fate in vitro revealed a remarkable resemblance between the behaviour of these cells and the PS in the embryo during gastrulation. Further molecular analysis revealed that the motility of PS-like cells was associated with a transient expression of the transcription factor Brachyury and was driven by the Wnt/beta-Catenin signalling pathway. Insight into the differentiation decision by ES cells in culture disclosed an inherent bias towards an anterior neuroectoderm fate while their ability to generate mesoderm increased with time. Quantitative analysis of the transcriptional dynamics underlying the two fates unveiled a mutual repression circuit controlled by Fgf/MAPK signalling. This is speculated to balance the proportions of cells with specific fates. In another part of the project, scientists studied the dynamics of division and differentiation of pancreatic progenitor cells. Results suggested that the timing during the cell cycle of endocrine differentiation initiation determined the progenitor division mode. Overall, the project results offered unparalleled insight into the molecular events over time responsible for cell specification during development. Furthermore, the temporal nature of gene expression regulation emphasised the controlled yet delicate nature of development.
Keywords
Development, CELLCOORDINATION, ES cells, primitive streak, Wnt/beta-Catenin signalling
