Two sequential gene expression programs bridged by cell division support long-distance collective cell migration.

The precise assembly of tissues and organs relies on spatiotemporal regulation of gene expression to coordinate cells' collective behavior. In Drosophila embryos, the midgut musculature is formed through collective migration of caudal visceral mesoderm (CVM) cells, but how gene expression changes as cells migrate is not well understood. Here, we focused on ten genes expressed in the CVM and cis-regulatory sequences controlling their expression. While some genes are continuously expressed, others are expressed only early or late during migration. Late expression relates to cell cycle progression, as driving string/Cdc25 causes earlier division of CVM cells and accelerates the transition to late gene expression. In particular, we found that cell cycle effector transcription factor E2f1 is a required input for late gene CG5080. Furthermore, while late genes are broadly expressed in all CVM cells, early gene transcripts are polarized to anterior or posterior ends of the migrating collective. We show this polarization requires transcription factors Snail, Zfh1, and Dorsocross. Collectively, these results identify two sequential gene expression programs bridged by cell division that support long-distance directional migration of CVM cells.