MAPK signaling in equations and embryos
May 6, Wed 2009
1:00 pm, MRB 200 Conference Room
Dr. Stas Shvartsman
Associate Professor of Chemical Engineering and the Lewis Sigler Institute for Integrative Genomics, Princeton University
Developmental patterning relies on combinatorial action of inductive cues and employs a number of strategies for signal integration. These include regulation of a single gene by multiple transcription factors and biochemical modification of a single transcription factor by multiple enzymes. Using the early Drosophila embryo as a model, we show that signal integration can also be mediated by a simple enzymatic network. The anterior structures of Drosophila embryo are specified by two inductive signals. One of them, a homeodomain protein Bicoid, establishes the anteroposterior morphogen gradient. The second (terminal) signal is provided by the localized activation of the MAPK pathway at both anterior and posterior poles. Activated MAPK phosphorylates the uniformly distributed transcriptional repressors Capicua and Groucho, relieving their repression of the terminal gap genes. At the anterior pole, MAPK phosphorylates Bicoid, potentiating its transcriptional effects. We demonstrate that modification of Bicoid by MAPK has a reverse effect on MAPK phosphorylation and signaling. In the resulting model, MAPK substrates compete for access to this kinase, establishing an enzyme-substrate competition network that integrates the anterior and terminal signals.
This work is done in collaboration with Yoosik Kim, Mathieu Coppey, Leiore Ajuria, Gerardo Jiménez, and Ze'ev Paroush.