Anisotropic Crb accumulation, modulated by Src42A, orients epithelial tube growth in Drosophila

Abstract

Size control of internal tubular organs, such as the lungs or vascular system, is critical for proper physiological activity and to prevent disease or malformations. This control incorporates the intrinsic physical anisotropy of tubes to generate proportionate organs that match their function. The exact mechanisms underlying tube size control and how tubular anisotropy is translated at the cellular level are still not fully understood. Here we investigate these mechanisms using the Drosophila tracheal system. We show that the apical polarity protein Crumbs transiently accumulates anisotropically at longitudinal cell junctions during tube elongation. We provide evidence indicating that the accumulation of Crumbs in specific apical domains correlates with apical surface growth. Hence, we propose that the anisotropic accumulation of Crb at the cellular level promotes a bias towards longitudinal membrane growth, orienting cell elongation and, as a consequence, longitudinal growth at the tissue level. We find that Src42A promotes Crb anisotropic accumulation, thereby identifying the first polarised cell behaviour downstream of Src42A. Our results indicate that Src42A activity favours a higher turnover of Crb protein at longitudinal junctions, possibly through a mechanism regulating protein trafficking and/or recycling. We propose a model where Src42A would sense the inherent anisotropic mechanical tension of the tube and translate it into a polarised Crumbs-mediated membrane growth, orienting longitudinal tube growth. This work provides new insights into the key question of how organ growth is controlled and polarised and unveils the function of two conserved proteins, Crumbs and Src42A, with important roles in development and homeostasis as well as in disease, in this biological process.