Identification of the mesoderm/endoderm interactions involved in murine liver and pancreas development

The definitive endoderm, one of the three primary germ layers, arises during gastrulation as a simple epithelial sheet that will produce the entire gut tube and associated organs including the thyroid, lung, liver and pancreas. DiI fate mapping and whole embryo culture were used to determine the endodermal origin of the 9.5 days post coitum (dpc) dorsal and ventral pancreas buds. Our results demonstrate that the progenitors of each bud occupy distinct endodermal territories. Similarly, previous data has shown that the neighboring liver is formed from two separate progenitor populations. Numerous studies have demonstrated that signals secreted from adjacent mesodermal tissues are required for appropriate induction of the endodermal organs, including the pancreas and liver buds. To determine the potential inductive tissue of the pancreas in vivo, we assessed the spatiotemporal association of the pancreas progenitors and neighboring tissues using a similar fate mapping strategy on tissues adjacent to the pancreas progenitors prior to and at the onset of induction. We found that these tissues are substantially anterior to the pancreas bud at E9.5, however, the extent of this dynamic migration in unique to distinct populations of mesodermal tissue. The notochord maintains a sustained interaction with the dorsal pancreas progenitors and repressive signals from the notochord have been implicated in the development of the dorsal pancreas in both mouse and chick. Additionally the mesenchyme that surrounds both dorsal and ventral pancreas buds is derived from coelomic mesothelium. We expanded our study to the liver, examining the fate of the progenitor populations which remain segregated and give rise to the rostral and caudal lobes, respectively. We found that the rostral lobe mesenchyme is derived from anterior splanchnic mesenchyme while the caudal lobe mesenchyme is also coelomic in origin. RNA sequencing of the rostral versus the caudal lobes indicates transcriptional differences between these populations of mesenchyme. Our data indicates that there may be two parallel pathways to the formation of functional hepatic tissue. As a whole our work gives insight on the development of the pancreas and the liver in vivo and supplies important data to the in vitro organ differentiation field