TY - JOUR
T1 - Interlocked feedforward loops control cell-type-specific rhodopsin expression in the drosophila eye
AU - Johnston, Robert J.
AU - Otake, Yoshiaki
AU - Sood, Pranidhi
AU - Vogt, Nina
AU - Behnia, Rudy
AU - Vasiliauskas, Daniel
AU - McDonald, Elizabeth
AU - Xie, Baotong
AU - Koenig, Sebastian
AU - Wolf, Reinhard
AU - Cook, Tiffany
AU - Gebelein, Brian
AU - Kussell, Edo
AU - Nakagoshi, Hideki
AU - Desplan, Claude
N1 - Funding Information:
We are very grateful to S. Britt, Y.N. Jan, C. Zuker, and the Bloomington Stock Center for reagents. We thank U. Alon, R. Carthew, O. Hobert, H. Johnston, P. O'Farrell, F. Payre, and E. Siggia for helpful comments on the manuscript. We thank all members of the Desplan laboratory for suggestions throughout the project. R.J.J. was supported by a Jane Coffin Childs Memorial Fund for Medical Research postdoctoral fellowship. N.V. was supported by Deutsche Forschungsgemeinschaft. R.B. was supported by the European Molecular Biology Organization and Human Frontier Science Program. D.V. was supported by NIH Grant 5F32EY016309-03. B.X. was supported by the University of Cincinnati Research Council. T.C. was supported by NIH Grant T32 HD046387 (ECM), Research to Prevent Blindness, and the Ziegler Foundation for the Blind. B.G. was supported by an NIH grant (GM079428). E.K. was supported by a Burroughs Wellcome Fund Career Award at the Scientific Interface. This work was funded by a grant from the National Eye Institute/NIH R01 13010 to C.D. and conducted in a facility constructed with the support of a Research Facilities Improvement Grant from the NCRR, NIH.
PY - 2011/6/10
Y1 - 2011/6/10
N2 - How complex networks of activators and repressors lead to exquisitely specific cell-type determination during development is poorly understood. In the Drosophila eye, expression patterns of Rhodopsins define at least eight functionally distinct though related subtypes of photoreceptors. Here, we describe a role for the transcription factor gene defective proventriculus (dve) as a critical node in the network regulating Rhodopsin expression. dve is a shared component of two opposing, interlocked feedforward loops (FFLs). Orthodenticle and Dve interact in an incoherent FFL to repress Rhodopsin expression throughout the eye. In R7 and R8 photoreceptors, a coherent FFL relieves repression by Dve while activating Rhodopsin expression. Therefore, this network uses repression to restrict and combinatorial activation to induce cell-type-specific expression. Furthermore, Dve levels are finely tuned to yield cell-type- and region-specific repression or activation outcomes. This interlocked FFL motif may be a general mechanism to control terminal cell-fate specification.
AB - How complex networks of activators and repressors lead to exquisitely specific cell-type determination during development is poorly understood. In the Drosophila eye, expression patterns of Rhodopsins define at least eight functionally distinct though related subtypes of photoreceptors. Here, we describe a role for the transcription factor gene defective proventriculus (dve) as a critical node in the network regulating Rhodopsin expression. dve is a shared component of two opposing, interlocked feedforward loops (FFLs). Orthodenticle and Dve interact in an incoherent FFL to repress Rhodopsin expression throughout the eye. In R7 and R8 photoreceptors, a coherent FFL relieves repression by Dve while activating Rhodopsin expression. Therefore, this network uses repression to restrict and combinatorial activation to induce cell-type-specific expression. Furthermore, Dve levels are finely tuned to yield cell-type- and region-specific repression or activation outcomes. This interlocked FFL motif may be a general mechanism to control terminal cell-fate specification.
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U2 - 10.1016/j.cell.2011.05.003
DO - 10.1016/j.cell.2011.05.003
M3 - Article
C2 - 21663797
AN - SCOPUS:79958279065
SN - 0092-8674
VL - 145
SP - 956
EP - 968
JO - Cell
JF - Cell
IS - 6
ER -