Temporal coordination of collective migration and lumen formation by antagonism between two nuclear receptors

Abstract

SummaryDuring development, cells often undergo multiple, distinct morphogenetic processes to form a tissue or organ, but how their temporal order and time interval are determined remain poorly understood. Here we show that the nuclear receptors E75 and DHR3 regulate the temporal order and time interval between the collective migration and lumen formation of a coherent group of about 8 cells called border cells during Drosophila oogenesis. In wild type egg chambers, border cells need to first collectively migrate to the anterior border of oocyte before undergoing lumen formation to form micropyle, the structure that is essential for sperm entry into the oocyte. We show that E75 is required for border cell migration and it antagonizes the activity of DHR3, which is necessary and sufficient for the subsequent lumen formation during micropyle formation. Furthermore, E75’s loss of function or DHR3 overexpression each leads to precocious lumen formation before collective migration, an incorrect temporal order for the two morphogenetic processes. Interestingly, both E75 and DHR3’s levels are simultaneously elevated in response to signaling from the EcR, a steroid hormone receptor that initiates border cell migration. Subsequently, the decrease of E75 levels in response to decreased EcR signaling leads to the de-repression of DHR3’s activity and hence switch-on of lumen formation, contributing to the regulation of time interval between collective migration and micropyle formation.