한빛사 논문
Abstract
Yoosik Kim,1María José Andreu,2 Bomyi Lim,1 Kwanghun Chung,3 Mark Terayama,4 Gerardo Jiménez,2 Celeste A. Berg,4 Hang Lu,3 and Stanislav Y. Shvartsman1,*
1Department of Chemical and Biological Engineering and Lewis-Sigler Institute for Integrative Genomics, Princeton University,Princeton, NJ 08544, USA
2Institut de Biologia Molecular de Barcelona-CSIC and Institucio´ Catalana de Recercai, Estudis Avancats, Parc Cientı´fic de Barcelona, Barcelona 08028, Spain
3School of Chemical and Biomolecular Engineering and Parker H. Petit Institute for Bioengineering and Bioscience, Georgia Institute of Technology, Atlanta, GA 30332, USA
4Department of Genome Sciences, University of Washington, Seattle, WA 98195-5065, USA
*Correspondence
Summary
Developing tissues are patterned by coordinated activities of signaling systems, which can be integrated by a regulatory region of a gene that binds multiple transcription factors or by a transcription factor that is modified by multiple enzymes. Based on a combination of genetic and imaging experiments in the early Drosophila embryo, we describe a signal integration mechanism that cannot be reduced to a single gene regulatory element or a single transcription factor. This mechanism relies on an enzymatic network formed by mitogen-activated protein kinase (MAPK) and its substrates. Specifically, anteriorly localized MAPK substrates, such as Bicoid, antagonize MAPK-dependent downregulation of Capicua, a repressor that is involved in gene regulation along the dorsoventral axis of the embryo. MAPK substrate competition provides a basis for ternary interaction of the anterior, dorsoventral, and terminal patterning systems. A mathematical model of this interaction can explain gene expression patterns with both anteroposterior and dorsoventral polarities.
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