Terminal regions of the Drosophila embryo are patterned by the localized activation of Mitogen Activated Protein Kinase (MAPK), which induces zygotic genes through relief of their repression by transcriptional repressor Capicua. The levels of MAPK activation at the anterior and posterior termini are close to each other, but the expression patterns of MAPK-target genes, such as zerknüllt (zen) and tailless (tll), display strong anterior-posterior (AP) asymmetry. This region-specific response to MAPK activation provides a clear example of context-dependent interpretation of inductive signaling, a common developmental effect that remains poorly understood. In the past, the AP asymmetry of zen expression was attributed to a mechanism that depends on MAPK substrate competition. We present data suggesting that the asymmetric expression of tll is generated by a different mechanism, based on feedforward control and multiple enhancers of the tll gene. A simple mathematical model of this mechanism correctly predicts how the wild-type expression pattern of tll changes in mutants affecting the anterior, dorsoventral, and terminal patterning systems and some of their direct targets.
This research was supported by grant from the National Institutes of Health [R01GM086537]. Y.K. was also supported by the T.J. Park Postdoctoral Fellowship. S.Y.S. and Y.K. thank Oliver Grimm, Yogi Jaeger, Gerardo Jimenez, Mike Levine, Ze'ev Paroush, and Eric Wieschaus for supplying flies and helpful discussions during the course of this work.
I. INTRODUCTION II. MATERIALS AND METHODS A. Fly strains B. In situ hybridization and immunohistochemistry C. Microscopy and image processing D. Quantification of gene expression boundaries E. Mathematical model III. EXPERIMENTAL RESULTS A. Dual control of anterior expression of tll by Bcd and Cic B. Hkb as a potential regulator of tll C. Dorsoventral control of tll expression D. Cic gradient as a regulator of posterior domains of tll and hkb E. Conceptual model of gene expression at the poles IV. MATHEMATICAL MODEL V. CONCLUSIONS AND DISCUSSIONS