Interpretation of Dynamic Signals: How Genes Respond When the Signal Changes

Tumorigenesis, stem cell maintenance and differentiation, and tissue patterning are all inherently multicellular phenomena that rely heavily on cell-cell communication processes.  However, most engineering approaches to these problems have focused on single-celled organisms, or, at best, aggregates of single-celled organisms. Bona-fide multicellular models organisms are also necessary to fully understand cell-cell signaling in its native context.  Therefore, to uncover the fundamental physical and biological principles behind cell-cell signaling, we study tissue patterning in the early embryo of the fruit fly Drosophila melanogaster.  In particular, we are studying how a spatially-distributed chemical signal patterns the dorsal-ventral axis of the embryo in the first several hours of development.  This chemical signal is a transcription factor called Dorsal, and the nuclei in the early embryo respond to Dorsal in a concentration-dependent fashion: their differentiation state is determined by the amount of Dorsal they are exposed to [1].  Recent work has shown that the strength of this signal varies appreciably in time, raising the question of how nuclei can reliably read a constantly-changing signal and differentiate accordingly [2-4].  Detailed studies of gene expression patterns reveal that nuclei respond to Dorsal in a real-time fashion, changing along with the changing signal.  This finding has implications for understanding the dynamics of gene expression when exposed to transient stimuli in the context of a multicellular organism.  One important implication is the ability of the embryo to respond to errors in gene expression patterns, in that if patterns are initially specified incorrectly, enough time and plasticity are available for correction.  Endnotes: [1] Roth, S.; Stein, D. & Nüsslein-Volhard, C. (1989). Cell, 59: 1189-1202. [2] Liberman, L. M.; Reeves, G. T. & Stathopoulos, A. (2009). Proc Natl Acad Sci U S A, 106: 22317-22322. [3] Delotto, R.; Delotto, Y.; Steward, R. & Lippincott-Schwartz, J. (2007). Development, 134: 4233-4241. [4] Reeves, G. T., et al. (2011). In preparation.