JAK/STAT controls organ size and fate specification by regulating morphogen production and signalling

Carles Recasens-Alvarez,Marco Milán,Ana Ferreira

doi:10.1038/ncomms13815

Abstract

A stable pool of morphogen-producing cells is critical for the development of any organ or tissue. Here we present evidence that JAK/STAT signalling in the Drosophila wing promotes the cycling and survival of Hedgehog-producing cells, thereby allowing the stable localization of the nearby BMP/Dpp-organizing centre in the developing wing appendage. We identify the inhibitor of apoptosis dIAP1 and Cyclin A as two critical genes regulated by JAK/STAT and contributing to the growth of the Hedgehog-expressing cell population. We also unravel an early role of JAK/STAT in guaranteeing Wingless-mediated appendage specification, and a later one in restricting the Dpp-organizing activity to the appendage itself. These results unveil a fundamental role of the conserved JAK/STAT pathway in limb specification and growth by regulating morphogen production and signalling, and a function of pro-survival cues and mitogenic signals in the regulation of the pool of morphogen-producing cells in a developing organ.

Highlights

A stable pool of morphogen-producing cells is critical for the development of any organ or tissue
We first monitored at this developmental stage the expression of Unpaired 1 (Upd) using upd-gal[4], a P-element insertion in the upd locus carrying the Gal[4] transcriptional activator[24], and the activity of the pathway using the 10xSTAT-GFP reporter[25]
We used the scalloped-gal[4] driver, which is expressed at high levels in the entire early wing primordium[8], to drive expression of RNA interference (RNAi) forms against the Drosophila Upd receptor (Domeless), JAK kinase (Hop) and STAT transcription factor (STAT92E)

Summary

Introduction

A stable pool of morphogen-producing cells is critical for the development of any organ or tissue. In development, localized expression of Unpaired and graded activity of the JAK/STAT pathway along the proximal– distal axis restrict the expression of genes regulated by the Vn/EGFR pathway to the body wall, ensuring wing fate specification by the activity of Wg. Later in development, JAK/STAT controls organ growth by promoting the survival and cycling of Hh-producing cells, thereby allowing stable expression of the Dpp stripe in the centre of the wing appendage. The building of the wing hinge—a cell population that isolates the growing appendage from the surrounding body wall and that is maintained by the activity of JAK/STAT18,19,23—contributes to delimiting the organizing activity of Dpp to the growing appendage Overall, these data reveal a novel role of the JAK/ STAT signalling pathway in the control of organ size and fate specification by regulating the production and activity of morphogens and by spatially restricting their organizing and growth-promoting functions. These findings add a new member to the ample repertoire of signalling molecules and corresponding pathways involved in limb development and unveil a role of prosurvival cues and mitogenic signals in limb development

Methods

Results

Conclusion