(155b) Tissue Patterning of Early Drosophila Embryos

To seek the understanding to build synthetic tissues from the ground up, we must first uncover the fundamental physical and biological principles behind tissue patterning in vivo. In a developing organism, tissue patterning relies extensively on mechanisms of cell-cell communication. While the cell is inherently complex, the manner in which cells communicate with each other to establish long-range patterns of gene expression in developing embryos ? patterns which eventually give rise to organs and structures ? simply adds another level of complexity to the problem. More than four decades ago, Lewis Wolpert proposed a model in which a concentration gradient of a diffusible chemical signal could be responsible for these patterns [1]. However, it appears that more is needed than simply a chemical system with diffusion from a local source and global degradation. To discern more about the physical mechanisms by which nature patterns developing tissues, we turn to the early embryo of the fruit fly, Drosophila melanogaster, where several instances of a graded chemical signal have been discovered [2,3]. We study the properties of the Drosophila NF-κB homologue, Dorsal, a maternally-provided transcription factor. A ventral-to-dorsal gradient in nuclear Dorsal concentration is established in the early embryo, and this gradient is responsible for the correct patterning of the DV axis. In previous work [4], we measured the Dorsal nuclear gradient as well as gene expression data of known Dorsal target genes and found results conflicting with Wolpert's long-standing model of tissue patterning. To dig deeper, we have studied a Dorsal-GFP fusion protein in live, developing embryos, and found the dynamics of Dorsal signaling to be more rapid than originally predicted. This implies that nuclei in the embryo must measure not only the local concentration of the chemical signal but also the time history of the signal. These observed dynamics are consistent with other recent studies of the Dorsal gradient [5,6]. Finally, we investigate more sophisticated models of tissue patterning in which the graded signal instructs a complex circuit diagram of genetic interactions, which in turn regulate the spatial output of gene expression patterns [7]. Endnotes: [1] Wolpert, L. (1969) J Theor Biol 25: 1-47. [2] Driever, W. & Nüsslein-Volhard, C. (1988). Cell, 54: 95-104. [3] Roth, S.; Stein, D. & Nüsslein-Volhard, C. (1989). Cell, 59: 1189-1202. [4] Liberman, L. M.; Reeves, G. T. & Stathopoulos, A. (2009). Proc Natl Acad Sci U S A, 106: 22317-22322. [5] Delotto, R.; Delotto, Y.; Steward, R. & Lippincott-Schwartz, J. (2007). Development, 134: 4233-4241. [6] Kanodia, J. S.; Rikhy, R.; Kim, Y.; Lund, V. K.; DeLotto, R.; Lippincott-Schwartz, J. & Shvartsman, S. Y. (2009). Proc Natl Acad Sci U S A, 106: 21707-21712. [7] Manu; Surkova, S.; Spirov, A. V.; Gursky, V. V.; Janssens, H.; Kim, A.; Radulescu, O.; Vanario-Alonso, C. E.; Sharp, D. H.; Samsonova, M. & Reinitz, J. (2009). PLoS Biol, 7: e1000049.