Drosophila Heat Shock Factor (HSF) Regulates Developmental Growth by Maintaining the Basal Expression of HSP83/HSP90

Abstract

The heat shock transcription factor HSF1 is best known as a master regulator of the proteotoxic stress response, yet its functions in animal development remain incompletely defined. In Drosophila melanogaster, heat shock factor (HSF) is essential for viability, but the mechanisms by which it promotes development are unclear. Here, we show that Hsf null larvae arrest at the early 2nd instar stage and exhibit a significant reduction in basal levels of the chaperone HSP83/HSP90. Tissue-specific knockdown of Hsf revealed widespread and organ-specific requirements, including defects in endoreplication and cell growth in larval prothoracic and salivary glands, adult wing defects following larval imaginal disc perturbation, follicle degeneration in the ovary, and melanotic tumor upon hemocyte depletion. In these tissues, loss of HSF typically leads to reduced HSP83 levels, and restoration of HSP83 expression partially or fully rescues these defects. These findings identify HSP83 as a critical downstream effector of HSF and demonstrate that HSF promotes development largely by maintaining basal chaperone expression. Together, our results establish HSF as a key regulator of developmental progression and highlight a central role for proteostasis in supporting tissue growth under non-stress conditions.