A conserved notochord enhancer controls pancreas development in vertebrates

The notochord is an evolutionary novelty in vertebrate evolution, functioning as an important signaling center during development. Notochord ablation experiments in chicken demonstrated that the notochord is crucial for pancreas development, however the molecular mechanism is not fully described. We show that the loss-of-function of nog2 in zebrafish, a Bmp antagonist expressed in the notochord, impairs beta-cell differentiation, compatible with the antagonistic role of Bmp in beta-cell differentiation. We also show that nog2 expression in the notochord is induced by at least one notochord enhancer and its loss-of-function is sufficient to impair beta-cell differentiation. Tracing Nog2 diffusion, we show that Nog2 emanates from the notochord to the pancreas progenitor domain. Finally, we found a notochord enhancer in the human and mice Nog genomic landscapes, suggesting that the acquisition of a Nog notochord enhancer occurred early in the vertebrate phylogeny, contributing for the development of complex organs such as the pancreas.