i3S (Instituto de Investigação e Inovação em Saúde), Universidade do Porto, Porto, Portugal; IBMC (Instituto de Biologia Molecular e Celular), Universidade do Porto, Porto, Portugal.
CABD (Centro Andaluz de Biología del Desarrollo), Universidad Pablo de Olavide, Seville, Spain.
Cell Rep. 2020 Jul 7;32(1):107862. doi: 10.1016/j.celrep.2020.107862.
The notochord is an evolutionary novelty in vertebrates that functions as an important signaling center during development. Notochord ablation in chicken has demonstrated that it is crucial for pancreas development; however, the molecular mechanism has not been fully described. Here, we show that in zebrafish, the loss of function of nog2, a Bmp antagonist expressed in the notochord, impairs β cell differentiation, compatible with the antagonistic role of Bmp in β cell differentiation. In addition, we show that nog2 expression in the notochord is induced by at least one notochord enhancer and its loss of function reduces the number of pancreatic progenitors and impairs β cell differentiation. Tracing Nog2 diffusion, we show that Nog2 emanates from the notochord to the pancreas progenitor domain. Finally, we find a notochord enhancer in human and mice Nog genomic landscapes, suggesting that the acquisition of a Nog notochord enhancer occurred early in the vertebrate phylogeny and contributes to the development of complex organs like the pancreas.
脊索是脊椎动物中的一种进化 novelty，在发育过程中作为一个重要的信号中心发挥作用。鸡的脊索消融实验表明，它对胰腺发育至关重要；然而，其分子机制尚未完全描述。在这里，我们表明在斑马鱼中，Bmp 拮抗剂 nog2 在脊索中的功能丧失会损害β细胞分化，这与 Bmp 在β细胞分化中的拮抗作用一致。此外，我们表明脊索中的 nog2 表达至少受到一个脊索增强子的诱导，其功能丧失会减少胰腺祖细胞的数量并损害β细胞分化。追踪 Nog2 的扩散，我们表明 Nog2 从脊索散发到胰腺祖细胞区域。最后，我们在人类和小鼠的 Nog 基因组景观中发现了一个脊索增强子，这表明脊椎动物进化早期获得了 Nog 脊索增强子，并有助于像胰腺这样的复杂器官的发育。
