Overexpression of lunatic fringe does not affect epithelial cell differentiation in the developing mouse lung.

Overexpression of lunatic fringe does not affect epithelial cell differentiation in the developing mouse lung.
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lunatic fringe的过度表达不会影响发育中的小鼠肺中的上皮细胞分化。

DOI:
10.1152/ajplung.00247.2004
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发表时间:
2005
期刊:
American journal of physiology. Lung cellular and molecular physiology
影响因子:
--
通讯作者:
M. Post
M. Post
中科院分区:
--
文献类型:
--
作者:
M. van Tuyl;F. Groenman;M. Kuliszewski;R. Ridsdale;Jinxia Wang;D. Tibboel;M. Post

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Notch/Notch-配体途径调节各种组织中的细胞命运决定和模式。它的几种成分在发育中的肺中表达,表明该途径对于气道细胞模式很重要。调节Notch信号传导的边缘蛋白对于定义多个器官的形态发生边界至关重要。它们在控制沿气道前后轴的细胞分化中的作用尚不清楚。在此,我们报告了小鼠肺发育过程中 Lunatic fringe (Lfng) 和 Notch 调节的基本螺旋-环-螺旋因子 Hes1 和 Mash-1 的时空表达模式。 Lfng 仅在早期发育期间在较大气道内衬的上皮细胞中表达。这些上皮细胞也表达 Hes1,但在妊娠后期,Hes1 表达仅限于终末细支气管内衬的上皮。 Mash-1表现出非常有特色的表达模式。它跟随早期肺中的神经嵴迁移,而在后期,Mash-1 在肺神经内分泌细胞中表达。为了阐明 Lfng 是否影响气道细胞分化,Lfng 在发育中的小鼠肺的远端上皮细胞中过度表达。 Lfng 的过度表达不影响 Hes1 和 Mash-1 的空间或时间表达。 Lfng 过度表达不会改变神经内分泌 CGRP 和蛋白质基因产物 9.5 的表达。近端纤毛细胞(β-微管蛋白 IV)、非纤毛细胞(CCSP)和远端上皮细胞(SP-C、T1α)标记物的表达也不受 Lfng 过量的影响。 Lfng 的过表达对间充质细胞标志物(α-sma、vWF、PECAM-1)表达没有影响。总的来说,数据表明 Lunatic 边缘在决定胎儿气道上皮细胞命运方面并没有发挥重要作用。
The Notch/Notch-ligand pathway regulates cell fate decisions and patterning in various tissues. Several of its components are expressed in the developing lung, suggesting that this pathway is important for airway cellular patterning. Fringe proteins, which modulate Notch signaling, are crucial for defining morphogenic borders in several organs. Their role in controlling cellular differentiation along anterior-posterior axis of the airways is unknown. Herein, we report the temporal-spatial expression patterns of Lunatic fringe (Lfng) and Notch-regulated basic helix-loop-helix factors, Hes1 and Mash-1, during murine lung development. Lfng was only expressed during early development in epithelial cells lining the larger airways. Those epithelial cells also expressed Hes1, but at later gestation Hes1 expression was confined to epithelium lining the terminal bronchioles. Mash-1 displayed a very characteristic expression pattern. It followed neural crest migration in the early lung, whereas at later stages Mash-1 was expressed in lung neuroendocrine cells. To clarify whether Lfng influences airway cell differentiation, Lfng was overexpressed in distal epithelial cells of the developing mouse lung. Overexpression of Lfng did not affect spatial or temporal expression of Hes1 and Mash-1. Neuroendocrine CGRP and protein gene product 9.5 expression was not altered by Lfng overexpression. Expression of proximal ciliated (beta-tubulin IV), nonciliated (CCSP), and distal epithelial cell (SP-C, T1alpha) markers also was not influenced by Lfng excess. Overexpression of Lfng had no effect on mesenchymal cell marker (alpha-sma, vWF, PECAM-1) expression. Collectively, the data suggest that Lunatic fringe does not play a significant role in determining cell fate in fetal airway epithelium.
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