Li Shuai, Francisco Adam B, Munroe Robert J, Schimenti John C, Long Qiaoming
Department of Animal Science, College of Agriculture and Life Sciences, Cornell University, Ithaca, NY 14850, USA.
BMC Dev Biol. 2010 Feb 19;10:19. doi: 10.1186/1471-213X-10-19.
The vertebrate pancreas contains islet, acinar and ductal cells. These cells derive from a transient pool of multipotent pancreatic progenitors during embryonic development. Insight into the genetic determinants regulating pancreatic organogenesis will help the development of cell-based therapies for the treatment of diabetes mellitus. Suppressor enhancer lin12/Notch 1 like (Sel1l) encodes a cytoplasmic protein that is highly expressed in the developing mouse pancreas. However, the morphological and molecular events regulated by Sel1l remain elusive.
We have characterized the pancreatic phenotype of mice carrying a gene trap mutation in Sel1l. We show that Sel1l expression in the developing pancreas coincides with differentiation of the endocrine and exocrine lineages. Mice homozygous for the gene trap mutation die prenatally and display an impaired pancreatic epithelial morphology and cell differentiation. The pancreatic epithelial cells of Sel1l mutant embryos are confined to the progenitor cell state throughout the secondary transition. Pharmacological inhibition of Notch signaling partially rescues the pancreatic phenotype of Sel1l mutant embryos.
Together, these data suggest that Sel1l is essential for the growth and differentiation of endoderm-derived pancreatic epithelial cells during mouse embryonic development.
脊椎动物的胰腺包含胰岛、腺泡和导管细胞。这些细胞在胚胎发育过程中源自一个短暂的多能胰腺祖细胞库。深入了解调节胰腺器官发生的遗传决定因素将有助于开发基于细胞的糖尿病治疗方法。抑制增强子lin12/Notch 1样蛋白（Sel1l）编码一种在发育中的小鼠胰腺中高度表达的细胞质蛋白。然而，由Sel1l调节的形态学和分子事件仍不清楚。
我们已经对携带Sel1l基因陷阱突变的小鼠的胰腺表型进行了特征描述。我们发现发育中的胰腺中Sel1l的表达与内分泌和外分泌谱系的分化相一致。基因陷阱突变的纯合小鼠在出生前死亡，并表现出胰腺上皮形态和细胞分化受损。在整个二次转变过程中，Sel1l突变胚胎的胰腺上皮细胞局限于祖细胞状态。Notch信号通路的药理学抑制部分挽救了Sel1l突变胚胎的胰腺表型。
总之，这些数据表明Sel1l在小鼠胚胎发育过程中对内胚层来源的胰腺上皮细胞的生长和分化至关重要。
