Citation:
Cell Rep. 2016 Jun 15. pii: S2211-1247(16)30658-1. doi: 10.1016/j.celrep.2016.05.060. [Epub ahead of print]
Abstract:
Organogenesis of the trachea and lungs requires a complex series of mesoderm-endoderm interactions mediated by WNT, BMP, retinoic acid (RA), and hedgehog (Hh), but how these pathways interact in a gene regulatory network is less clear. Using Xenopus embryology, mouse genetics, and human ES cell cultures, we identified a conserved signaling cascade that initiates respiratory lineage specification. We show that RA has multiple roles; first RA pre-patterns the lateral plate mesoderm and then it promotes Hh ligand expression in the foregut endoderm. Hh subsequently signals back to the pre-patterned mesoderm to promote expression of the lung-inducing ligands Wnt2/2b and Bmp4. Finally, RA regulates the competence of the endoderm to activate the Nkx2-1+ respiratory program in response to these mesodermal WNT and BMP signals. These data provide insights into early lung development and a paradigm for how mesenchymal signals are coordinated with epithelial competence during organogenesis.
Epub:
Yes
Link to Publication:
http://www.sciencedirect.com/science/article/pii/S2211124716306581
Organism or Cell Type:
Xenopus
Delivery Method:
microinjection