Gene Regulation by MAPK Substrate Competition

Dev Cell. 2011 Jun 14;20(6):880-7. doi: 10.1016/j.devcel.2011.05.009.

Abstract

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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Animals
  • Drosophila Proteins / metabolism*
  • Drosophila melanogaster / embryology
  • Drosophila melanogaster / metabolism*
  • Embryo, Nonmammalian / cytology
  • Embryo, Nonmammalian / metabolism*
  • Female
  • Gene Expression Regulation, Developmental*
  • HMGB Proteins / metabolism*
  • Homeodomain Proteins / metabolism*
  • Immunoenzyme Techniques
  • In Situ Hybridization
  • Mitogen-Activated Protein Kinases / antagonists & inhibitors
  • Mitogen-Activated Protein Kinases / metabolism*
  • Models, Theoretical
  • Phosphorylation
  • Repressor Proteins / metabolism*
  • Signal Transduction
  • Trans-Activators / metabolism*

Substances

  • Drosophila Proteins
  • HMGB Proteins
  • Homeodomain Proteins
  • Repressor Proteins
  • Trans-Activators
  • Zen protein, Drosophila
  • bcd protein, Drosophila
  • cic protein, Drosophila
  • Mitogen-Activated Protein Kinases