Control of Organ Size and Shape During the Differential Development of Wing and Haltere in Drosophila

Abstract

Diverse organ shapes and sizes arise from the complex interplay between cellular properties, mechanical forces, and gene regulation. Drosophila wing- a flat structure and the globular haltere are two homologous flight appendages emerging from a similar group of progenitor cells. The activity of a single Hox transcription factor, Ultrabithorax (Ubx), governs the development of these two distinct organs- wing and haltere with different cell and organ morphologies. Studying the differential development of wing and haltere presents a unique paradigm for understanding the complexities of organogenesis and how Hox genes modulate different signalling pathways and cellular processes, thereby influencing morphogenesis to mould different cell and organ shapes. Our studies on differential development of wing and haltere shapes suggest that the localisation and abundance of actomyosin complexes, apical cell contractility, properties of extracellular matrix, and cell size and shape, which is a result of various cell intrinsic and extrinsic forces, can influence the flat vs. globular geometry of these two organs. Our data indicate that the columnar cells of the wing and haltere discs are mechanically different. Loss of Ubx function led to reversed cellular features and increased actomyosin accumulation in haltere discs, mimicking wing cell-like characteristics at the cellular and organ levels. We observed that RNAi-mediated downregulation of Atrophin (also known as Grunge) or Pten, in the background of downregulated expanded (resulting in elevated Yorkie (Yki), gives significant overgrowth in halteres. These mutants also induced a change in the cell dimensions, increase in cell apical contractility and actomyosin levels in halteres. The mutant adult halteres exhibited increased capitellum, size, flatter morphology, ECM remodelling, and changes in cellular architecture, leading to a partial haltere to wing homeotic transformation. We also observed deformations in the three-dimensional architecture of the mutant halteres during early pupal morphogenesis, indicating the role of the above-mentioned factors in force generation and in driving differential morphogenesis, leading to different organ shapes. When combined with computational modelling, these approaches now permit us to understand the relative contributions of cell size and shape changes and various inter- and intra-cellular forces to the overall change in the tissue shape. The study provides insights into the cellular mechanisms underlying the differential development and conferring the shape of the wing and haltere. Taken together, our study enhances our understanding of how small changes in cellular physical properties, gene expression and cell-cell, cell-ECM interactions modulated by Ubx can lead to the development of distinct structures.