Pancreatic Ductal Morphogenesis and the Pdx1 Homeodomain Transcription Factor

被引:36
作者
Wescott, Melanie P. [1 ,3 ]
Rovira, Meritxell [6 ,7 ,8 ]
Reichert, Maximilian [1 ,3 ]
von Burstin, Johannes [1 ,3 ]
Means, Anna [4 ,5 ]
Leach, Steven D. [3 ]
Rustgi, Anil K. [1 ,2 ,3 ]
机构
[1] Univ Penn, Dept Med, Div Gastroenterol, Philadelphia, PA 19104 USA
[2] Univ Penn, Dept Genet, Philadelphia, PA 19104 USA
[3] Univ Penn, Abramson Canc Ctr, Philadelphia, PA 19104 USA
[4] Vanderbilt Univ, Dept Surg, Nashville, TN 37232 USA
[5] Vanderbilt Univ, Dept Cell & Dev Biol, Nashville, TN 37232 USA
[6] Johns Hopkins Univ, McKusick Nathans Inst Genet Med, Dept Surg, Baltimore, MD 21205 USA
[7] Johns Hopkins Univ, McKusick Nathans Inst Genet Med, Dept Oncol, Baltimore, MD 21205 USA
[8] Johns Hopkins Univ, McKusick Nathans Inst Genet Med, Dept Cell Biol, Baltimore, MD 21205 USA
基金
美国国家卫生研究院;
关键词
EPITHELIAL-MESENCHYMAL TRANSITION; BRANCHING MORPHOGENESIS; INDUCED TUBULOGENESIS; DUODENAL HOMEOBOX-1; CELLS; GROWTH; MICE; KI-RAS(G12V); MECHANISMS; EXPRESSION;
D O I
10.1091/mbc.E09-03-0203
中图分类号
Q2 [细胞生物学];
学科分类号
071009 ; 090102 ;
摘要
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.
引用
收藏
页码:4838 / 4844
页数:7
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