Premature differentiation and aberrant movement of pituitary cells lacking both Hes1 and Prop1.
Premature differentiation and aberrant movement of pituitary cells lacking both Hes1 and Prop1.
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DOI：
10.1016/j.ydbio.2008.10.010
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发表时间：
2009-01-01
影响因子：
2.7
通讯作者：
Raetzman, Lori T.
中科院分区：
文献类型：
--
作者：
Himes, Ashley D.;Raetzman, Lori T.
在垂体中，从增殖的祖细胞到分化的激素产生细胞的转变以时间依赖性和空间受限的方式被仔细地调节。我们报告说，两个目标的Notch信号，Hes 1和Prop 1，需要保持祖细胞内Rathke的袋和限制分化细胞的腹侧垂体。我们观察到ACTH和αGSU产生细胞在Rathke囊沿着过早分化，只有当Prop 1和Hes 1都丢失时，Mash 1才异位表达。我们还发现，当细胞从Rathke囊过渡到前叶时，细胞中N-钙粘蛋白表达的下调似乎对它们的运动至关重要。在Prop 1突变体中，细胞被困在Rathke囊中，N-钙粘蛋白表达仍然很高。此外，鼻涕虫，上皮细胞间质转化的标志物，是缺席的背前叶。当Hes 1在Prop 1突变体中丢失时，N-钙粘蛋白下调，细胞能够离开Rathke囊，但失去了它们的迁移线索，并在Rathke囊周围形成异位灶。我们的数据揭示了Hes 1和Prop 1在细胞分化和运动中的重要重叠功能，这些功能对垂体器官形成至关重要。
In the pituitary, the transition from proliferating progenitor cell into differentiated hormone producing cell is carefully regulated in a time dependent and spatially restricted manner. We report that two targets of Notch signaling, Hes1 and Prop1, are needed to maintain progenitors within Rathke’s pouch and for the restriction of differentiated cells to the ventral pituitary. We observed ACTH and αGSU producing cells that had prematurely differentiated within Rathke’s pouch along with correlated ectopic expression of Mash1 only when both Prop1 and Hes1 were lost. We also discovered that downregulation of N-cadherin expression in cells as they transition from Rathke’s pouch to the anterior lobe appears to be essential for their movement. In the Prop1 mutant, cells are trapped in Rathke’s pouch and N-cadherin expression remains high. Also, Slug, a marker of epithelial to mesenchymal transition, is absent in the dorsal anterior lobe. When Hes1 is lost in the Prop1 mutant, N-cadherin is downregulated and cells are able to exit Rathke’s pouch but have lost their migrational cues and form ectopic foci surrounding Rathke’s pouch. Our data reveal important overlapping functions of Hes1 and Prop1 in cell differentiation and movement that are critical for pituitary organogenesis.
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DOI：
10.1073/pnas.0510419103
发表时间：
2006-01-31
影响因子：
11.1
作者：
Ge, WH;He, F;Sun, YE
通讯作者：
Sun, YE
影响因子：
2.5
作者：
Douglas, KR;Brinkmeier, ML;Camper, SA
通讯作者：
Camper, SA
影响因子：
4
作者：
Bolós, V;Peinado, H;Cano, A
通讯作者：
Cano, A
影响因子：
2.7
作者：
Jiang, RL;Lan, Y;Gridley, T
通讯作者：
Gridley, T
影响因子：
2.7
作者：
Andersen, B;Pearse, RV;Rosenfeld, MG
通讯作者：
Rosenfeld, MG