Investigating responses to BMP signaling with in vivo optogenetics

Embryonic patterning is orchestrated by signaling molecules that activate different genes in the right place at the right time. How do signaling molecules generate diverse patterns of gene expression? In zebrafish, a gradient of the signaling molecule BMP patterns the dorsal-ventral axis. We identified genes activated by BMP and found that they have diverse spatiotemporal expression profiles. To understand why, we developed an optogenetic method to reversibly and tunably activate BMP signaling in vivo with light. We used this approach to test whether individual genes respond differently to BMP signaling, and whether those differences could explain their distinct expression profiles. We found that differential responses to BMP signaling alone did not explain the majority of the diversity in expression profiles. Instead, much of their expression diversity is explained by inputs from other signaling pathways, including Nodal and FGF. Our results challenge the basic “morphogen” model and support an alternative model in which gene expression is sculpted by the combined activity of multiple signaling pathways