Steroid hormone signaling synchronizes cell migration machinery, adhesion, and polarity to direct collective movement

Abstract

Migratory cells – either individually or in cohesive groups – are critical for spatiotemporally-regulated processes such as embryonic development and wound healing. Their dysregulation is the underlying cause of formidable health problems such as birth defects and metastatic cancers. Border cell behavior during Drosophila oogenesis provides an effective model to study temporally-regulated, collective cell migration in vivo. Developmental timing in flies is primarily controlled by the steroid hormone ecdysone, which acts through a well-conserved, nuclear hormone receptor complex. Ecdysone signaling determines the timing of border cell migration but the molecular mechanisms governing this remain obscure. We found that border cell clusters expressing a dominant negative form of ecdysone receptor extend ineffective protrusions. Additionally, these clusters have aberrant spatial distributions of E-cadherin, apical domain markers and activated myosin that do not overlap. Remediating their expression or activity individually in ecdysone signaling-mutant clusters did not restore proper migration. We propose that ecdysone signaling synchronizes the functional distribution of E-cadherin, atypical protein kinase C, Discs large, and activated myosin post-transcriptionally to coordinate adhesion, polarity, and contractility and temporally control collective cell migration.