Temporal Coordination of Collective Migration and Lumen Formation by Antagonism between Two Nuclear Receptors

During development, cells 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 cells named border cells during Drosophila oogenesis. We show that E75, in response to ecdysone signaling, antagonizes the activity of DHR3 during border cell migration, and DHR3 is necessary and sufficient for the subsequent lumen formation that is critical for micropyle morphogenesis. DHR3's lumen-inducing function is mainly mediated through βFtz-f1, another nuclear receptor and transcription factor. Furthermore, both DHR3 and βFtz-f1 are required for chitin secretion into the lumen, whereas DHR3 is sufficient for chitin secretion. Lastly, DHR3 and βFtz-f1 suppress JNK signaling in the border cells to downregulate cell adhesion during lumen formation.