Establishment of a Developmental Compartment Requires Interactions between Three Synergistic Cis-regulatory Modules.

Dimitri Bieli,Matthew Slattery,Paul Schedl,Fisun Hamaratoglu,Daryl Gohl,David Requena,Oguz Kanca,Martin Müller,Carlos Estella,Markus Affolter

doi:10.1371/journal.pgen.1005376

Abstract

The subdivision of cell populations in compartments is a key event during animal development. In Drosophila, the gene apterous (ap) divides the wing imaginal disc in dorsal vs ventral cell lineages and is required for wing formation. ap function as a dorsal selector gene has been extensively studied. However, the regulation of its expression during wing development is poorly understood. In this study, we analyzed ap transcriptional regulation at the endogenous locus and identified three cis-regulatory modules (CRMs) essential for wing development. Only when the three CRMs are combined, robust ap expression is obtained. In addition, we genetically and molecularly analyzed the trans-factors that regulate these CRMs. Our results propose a three-step mechanism for the cell lineage compartment expression of ap that includes initial activation, positive autoregulation and Trithorax-mediated maintenance through separable CRMs.

Highlights

Animal development requires the segregation of cell populations using both lineage and nonlineage boundaries
By dissecting the regulatory sequences required for ap expression, we solve this problem for this critical selector gene
We used a combination of experimental approaches to identify and functionally characterize the cis-regulatory modules (CRMs) that regulate

Summary

Introduction

Animal development requires the segregation of cell populations using both lineage and nonlineage boundaries. These cell boundaries act as signaling centers that organize the growth and patterning of specific tissues (reviewed in [1]). Ligands encoded by decapentaplegic (dpp) and wingless (wg) are secreted and activate signaling pathways that orchestrate wing development [2,3,4,5,6,7,8]. The generation of the A/P and D/V compartments is directed by specific transcription factors, the selector genes engrailed (en) and apterous (ap), respectively, that define the identity of the cells using a binary code (on or off) [9,10,11,12,13,14,15]. Since ap function is crucial to initiate the signaling center at the D/V boundary [20,21], ap null mutants completely lack the wing [16]

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Discussion

Conclusion