Molecular pathways in cell differentiation
The REGULATING FLIES (Physical principles of molecular signal integration in early fly development) project addressed the fundamental question of how molecular pathways for cell differentiation are controlled. They developed a technique for investigating the dynamics of transcription in the early stages of development in the fruit fly model organism. In fruit fly development, proteins sequentially turn on genes, whose expression lays out the blueprint for the segments of the insect’s body. The genes code for proteins, which carry out specific functions. The challenge was to understand how genes are turned on at the correct location and time during development to produce a functioning adult organism. Previous studies have shown that not all possible molecular pathways are realised in nature. Therefore, certain molecular solutions could be better suited for particular functions like noise reduction, information processing, or phenotypic variation within a population. These ideas were tested by REGULATING FLIES who developed a genetic toolbox that enabled detailed measurements to be conducted in fly embryos. Researchers analysed data from the fruit fly transcription process. After an initial period of inactivity following cell division (mitosis), transcription at the hunchback locus occurs in bursts with clear states of reduced and enhanced activity. Scientists also identified weak memory signatures of the transcriptional state between subsequent cell cycles. Using a very noisy system in fly development, the team identified for the first time, strong transcriptional memory in development. In addition, researchers studied the role of homeodomain proteins in the binding of transcription factor proteins such as bicoid to regulatory sites along the DNA. Bicoid specifies which end of the egg will become the insect’s head. REGULATING FLIES conducted experimental validation of molecular networks in fruit flies. Geneticists and biophysicists worked together to unravel the coordinated spatio-temporal expression of genes during development, describing their interactions quantitatively. This information will be ultimately used to determine the global physical principles underlying complex interactions.
Keywords
Differentiation, REGULATING FLIES, transcription, hunchback, homeodomain protein
