RTK signaling modulates the Dorsal gradient

Author:

Helman Aharon1,Lim Bomyi2,Andreu María José3,Kim Yoosik2,Shestkin Tatyana1,Lu Hang4,Jiménez Gerardo3,Shvartsman Stanislav Y.2,Paroush Ze’ev1

Affiliation:

1. Department of Developmental Biology and Cancer Research, IMRIC, Faculty of Medicine, The Hebrew University, Jerusalem 91120, Israel.

2. Department of Chemical and Biological Engineering and Lewis-Sigler Institute for Integrative Genomics, Princeton University, Princeton, NJ 08544, USA.

3. Institut de Biologia Molecular de Barcelona-CSIC and Institució Catalana de Recerca i Estudis Avançats, Parc Científic de Barcelona, 08028-Barcelona, Spain.

4. School of Chemical and Biomolecular Engineering and Parker H. Petit Institute for Bioengineering and Bioscience, Georgia Institute of Technology, Atlanta, GA 30332, USA.

Abstract

The dorsoventral (DV) axis of the Drosophila embryo is patterned by a nuclear gradient of the Rel family transcription factor, Dorsal (Dl), that activates or represses numerous target genes in a region-specific manner. Here, we demonstrate that signaling by receptor tyrosine kinases (RTK) reduces nuclear levels and transcriptional activity of Dl, both at the poles and in the mid-body of the embryo. These effects depend on wntD, which encodes a Dl antagonist belonging to the Wingless/Wnt family of secreted factors. Specifically, we show that, via relief of Groucho- and Capicua-mediated repression, the Torso and EGFR RTK pathways induce expression of WntD, which in turn limits Dl nuclear localization at the poles and along the DV axis. Furthermore, this RTK-dependent control of Dl is important for restricting expression of its targets in both contexts. Thus, our results reveal a new mechanism of crosstalk, whereby RTK signals modulate the spatial distribution and activity of a developmental morphogen in vivo.

Publisher

The Company of Biologists

Subject

Developmental Biology,Molecular Biology

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