Stem Cell and Pancreas Developmental Biology, Stem Cell Center, Department of Laboratory Medicine, Lund, Lund University, BMC B10 Klinikgatan 26, SE-221 84 Lund, Sweden.
Dev Biol. 2011 Apr 15;352(2):267-77. doi: 10.1016/j.ydbio.2011.01.026. Epub 2011 Jan 31.
Endoderm development is dependent on inductive signals from different structures in close vicinity, including the notochord, lateral plate mesoderm and endothelial cells. Recently, we demonstrated that a functional vascular system is necessary for proper pancreas development, and that sphingosine-1-phosphate (S1P) exhibits the traits of a blood vessel-derived molecule involved in early pancreas morphogenesis. To examine whether S1P(1)-signaling plays a more general role in endoderm development, S1P(1)-deficient mice were analyzed. S1P(1) ablation results in compromised growth of several foregut-derived organs, including the stomach, dorsal and ventral pancreas and liver. Within the developing pancreas the reduction in organ size was due to deficient proliferation of Pdx1(+) pancreatic progenitors, whereas endocrine cell differentiation was unaffected. Ablation of endothelial cells in vitro did not mimic the S1P(1) phenotype, instead, increased organ size and hyperbranching were observed. Consistent with a negative role for endothelial cells in endoderm organ expansion, excessive vasculature was discovered in S1P(1)-deficient embryos. Altogether, our results show that endothelial cell hyperplasia negatively influences organ development in several foregut-derived organs.
内胚层的发育依赖于来自附近不同结构的诱导信号，包括脊索、侧板中胚层和内皮细胞。最近，我们证明了一个功能性的血管系统对于胰腺的正常发育是必要的，而且鞘氨醇-1-磷酸（S1P）表现出一种血管来源的分子的特征，参与早期胰腺形态发生。为了研究 S1P（1）信号是否在更普遍的内胚层发育中发挥作用，我们分析了 S1P（1）缺陷小鼠。S1P（1）缺失导致几个前肠衍生器官的生长受损，包括胃、背侧和腹侧胰腺和肝脏。在发育中的胰腺中，器官大小的减小是由于 Pdx1（+）胰腺祖细胞的增殖不足，而内分泌细胞分化不受影响。体外内皮细胞的缺失并没有模拟 S1P（1）表型，而是观察到器官大小增加和分支过度。与内皮细胞在扩大内胚层器官中的负作用一致，在 S1P（1）缺陷胚胎中发现了过多的血管。总之，我们的结果表明内皮细胞增生会对几个前肠衍生器官的器官发育产生负面影响。
