BMP signaling modulations control primitive streak patterning

Abstract

The primitive streak (PS) is the embryonic structure from which mesoderm and definitive endoderm cells emerge to form organs and fetal tissues. The identities of the cells leaving the PS depend on both the time and the position at which they exit. Three signaling molecules, BMP4, WNT3 and NODAL, play key roles in determining these identities, but it has been difficult to disentangle the contribution of each to this process in the mouse embryo. Using 2D gastruloids that recapitulate early aspects of mouse gastrulation in vitro, we have previously shown that WNT3 and NODAL promote distal PS fates on their own, and proximal PS fates in the presence of BMP4. We now detail further the impact of BMP4 on the cell identities produced in gastruloids. Single cell RNA-seq analysis shows that prolonged exposure to BMP4 results in the presence of all the cell types, including primordial germ cells, which normally form from the most proximal part of the pluripotent epiblast. We then show that reducing the duration or intensity of gastruloid exposure to BMP4 can allow the emergence of more distal cell identities, such as paraxial mesoderm, alongside anterior PS derivatives. These results, which are consistent with embryological studies, provide key elements for understanding how the varied output of the PS is controlled.