Stafford David, Prince Victoria E
The Committee on Developmental Biology, Chicago, IL 60637, USA.
Curr Biol. 2002 Jul 23;12(14):1215-20. doi: 10.1016/s0960-9822(02)00929-6.
The mechanisms that subdivide the endoderm into the discrete primordia that give rise to organs such as the pancreas and liver are not well understood. However, it is known that retinoic acid (RA) signaling is critical for regionalization of the vertebrate embryo: when RA signaling is either prevented or augmented, anteroposterior (AP) patterning of the CNS and mesoderm is altered and major developmental defects occur. We have investigated the role of RA signaling in regionalization of the zebrafish endoderm. Using a mutant that prevents RA synthesis and an antagonist of the RA receptors, we show that specification of both the pancreas and liver requires RA signaling. By contrast, RA signaling is not required for the formation of the endodermal germ layer or for differentiation of other endodermal organs. Timed antagonist and RA treatments show that the RA-dependent step in pancreatic specification occurs at the end of gastrulation, significantly earlier than the expression of known markers of pancreatic progenitors. In addition to being required for pancreatic specification, RA has the capacity to transfate anterior endoderm to a pancreatic fate.
将内胚层细分为产生胰腺和肝脏等器官的离散原基的机制尚不清楚。然而，已知视黄酸（RA）信号传导对于脊椎动物胚胎的区域化至关重要：当RA信号传导被阻断或增强时，中枢神经系统和中胚层的前后（AP）模式会发生改变，并出现主要的发育缺陷。我们研究了RA信号传导在斑马鱼内胚层区域化中的作用。使用一种阻止RA合成的突变体和RA受体拮抗剂，我们发现胰腺和肝脏的特化都需要RA信号传导。相比之下，内胚层胚层的形成或其他内胚层器官的分化不需要RA信号传导。定时拮抗剂和RA处理表明，胰腺特化中依赖RA的步骤发生在原肠胚形成末期，比胰腺祖细胞已知标志物的表达要早得多。除了胰腺特化所需外，RA还具有将前端内胚层转化为胰腺命运的能力。
