Spatial and molecular anatomy of germ layers in the gastrulating Cynomolgus monkey embryo

Abstract

SummaryDuring mammalian embryogenesis, spatial regulation of gene expression and cell signaling are functionally coupled with lineage specification, patterning of tissue progenitors and germ layer morphogenesis. While the mouse model has been instrumental for our understanding of mammalian development, comparatively little is known about human and non-human primate gastrulation due to the restriction of both technical and ethical issues. Here, we present a morphological and molecular survey of spatiotemporal dynamics of cell types populating the non-human primate embryos during gastrulation. We performed serial sections of Cynomolgus monkeys (Macaca fascicularis) gastrulating embryos at 1-day temporal resolution from E17 to E21, and reconstructed three-dimensional digital models based on high-resolution anatomical atlas that revealed the dynamic changes in the geography of the mesoderm and primitive streaks. Spatial transcriptomics identified unique gene profiles that correspond to distinct germ layers and cross-species spatiotemporal transcriptome analysis revealed a developmental coordinate of germ layer segregation between mouse and primate. Furthermore, we identified species-specific transcription programs during gastrulation. These results offer important insights into evolutionarily conserved and divergent processes during mammalian gastrulation. HighlightA high-resolution anatomical atlas of Cynomolgus gastrulation embryosCreated a three-dimensional digital template from serial sections of five developmental stagesA two-dimensional spatiotemporal transcriptome of the germ layers of gastrulating embryosCross-species comparison infers conservation of functional attributes of regulome and signaling activity in germ layer formation