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要旨

Signaling molecules activate distinct patterns of gene expression to coordinate embryogenesis, but how spatiotemporal expression diversity is generated is an open question. In zebrafish, a BMP signaling gradient patterns the dorsal-ventral axis. We systematically identified BMP target genes with RNA-sequencing. Using lightsheet microscopy and NanoString molecular barcoding, we found that BMP target genes have diverse spatiotemporal expression patterns. Transcriptional responses to optogenetically generated high- and low- amplitude BMP signaling pulses suggest that spatiotemporal expression is not defined by different signaling activation thresholds. In addition, we observed negligible correlations between spatiotemporal expression and transcription kinetics in response to BMP signaling pulses. In contrast, spatial differences between BMP target genes largely collapsed when FGF and Nodal signaling were inhibited. Our results challenge the basic morphogen model and indicate that combinatorial signaling by BMP, FGF, and Nodal is a major driver of spatial diversity in BMP-dependent gene expression.