Pancreatic Ductal Morphogenesis and the Pdx1 Homeodomain Transcription Factor
Pancreatic Ductal Morphogenesis and the Pdx1 Homeodomain Transcription Factor
复制标题
DOI：
10.1091/mbc.e09-03-0203
复制
发表时间：
2009-11-15
影响因子：
3.3
通讯作者：
Rustgi, Anil K.
中科院分区：
文献类型：
--
作者：
Wescott, Melanie P.;Rovira, Meritxell;Rustgi, Anil K.
胰腺胚胎发育的特征是形态发生的早期阶段，在这个阶段，发育中的胰腺上皮的多能前体细胞产生各种成熟的外分泌和内分泌细胞类型。腺泡和胰岛细胞谱系的遗传决定因素在某种程度上是明确的；然而，指导导管形成和分化的分子机制仍有待阐明。复杂的胰腺导管结构是由称为分支形态发生或小管发生的前体细胞扩张和迁移的重复程序建立的，在小鼠发育过程中伴随着Pdx1转录因子的峰值表达。因此，我们评估了跨越导管形成关键时期的胰腺胚胎切片中Pdx1的表达，并发现了一组意外的非胰岛Pdx1阳性细胞群，显示出分支的物理特征。然后，我们建立了使用原代胰腺管细胞的分支形态发生的3D细胞培养模型，并鉴定了Pdx1表达的瞬时激增，这是分支细胞所特有的。根据这些观察，我们推测Pdx1可能在时间上参与了足以促进分支形态发生所需的生化和形态变化的基因表达程序。
Embryonic development of the pancreas is marked by an early phase of dramatic morphogenesis, in which pluripotent progenitor cells of the developing pancreatic epithelium give rise to the full array of mature exocrine and endocrine cell types. The genetic determinants of acinar and islet cell lineages are somewhat well defined; however, the molecular mechanisms directing ductal formation and differentiation remain to be elucidated. The complex ductal architecture of the pancreas is established by a reiterative program of progenitor cell expansion and migration known as branching morphogenesis, or tubulogenesis, which proceeds in mouse development concomitantly with peak Pdx1 transcription factor expression. We therefore evaluated Pdx1 expression with respect to lineage-specific markers in embryonic sections of the pancreas spanning this critical period of duct formation and discovered an unexpected population of nonislet Pdx1-positive cells displaying physical traits of branching. We then established a 3D cell culture model of branching morphogenesis using primary pancreatic duct cells and identified a transient surge of Pdx1 expression exclusive to branching cells. From these observations we propose that Pdx1 might be involved temporally in a program of gene expression sufficient to facilitate the biochemical and morphological changes necessary for branching morphogenesis.