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Apoptosis and epithelium-mesenchyme interaction during mammalian morphogenesis

哺乳动物形态发生过程中的细胞凋亡和上皮间质相互作用

基本信息

批准号：
07670012
负责人：
MORI Chisato
金额：
$ 1.47万
依托单位：
KYOTO UNIVERSITY
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
1995
资助国家：
日本
起止时间：
1995 至 1996
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-07670012/
关键词：
programd cell death morphogenesis apoptosis palate limb spermatogenesis gene abnormal development

项目摘要

Apoptosis is a common event during mammalian morphogenesis, which is morphologically known as programd cell death. The cell death in interdigital spaces of mammalian developing limb and the disappearance of the midline epithelial seam during the fusion process of the mammalian secondary palate are classical examples of morphogenetic programd cell death. For the formating of various structure during development, apoptosis has been considered to play a key role by elimination unnecessary cells to achieve complicated histogenesis and organogenesis. Our recent studies showed that apoptosis in the limb and palate development plays more aggressive roles in addition to the elimination of unnecessaery cells. In mammalian limb development, apoptosis may play a role in preventing the formation of extra digits and reducing the size of the first digit as well as in the digit separation and joint formation (Mori et al., 1995 ; Mori, 1995). In the process of palate fusion, apoptotic cell death may be required for the midline epithelial fusion of opposing palatal shelves (Mori et al., 1994). In addition, we examined the cause of limb malformations induced by BrdU in fetal mice and found that the altered expression of several genes including apoptosis-related genes, Hox genes and growth factor genes at the anterior region of the hindlimb bud in the formation of preaxial polydactyly and triphalangism of the first digit in BrdU-treated mouse fetuses. Moreover, our analysis of apoptosis in the testes of some testis-specific gene deficient mice showed that an additional increased level of apoptosis during the first wave of spermatogenesis, in pachytene spematocytes (Mori et al., 1997). further studies will be necessary to define clearly the significance of apoptosis during mammalian morphogenesis.

细胞凋亡是哺乳动物形态发生过程中的常见事件，在形态上被称为程序性细胞死亡。哺乳动物发育肢体指间间隙的细胞死亡和哺乳动物次级腭部融合过程中中线上皮缝的消失是形态发生程序性细胞死亡的经典例子。对于发育过程中各种结构的形成，细胞凋亡被认为起着关键作用，它通过消除不必要的细胞来实现复杂的组织发生和器官发生。我们最近的研究表明，除了消除不必要的细胞外，细胞凋亡在四肢和腭部发育中发挥着更积极的作用。在哺乳动物肢体发育中，细胞凋亡可能在防止额外手指的形成、减小第一个手指的大小以及手指分离和关节形成方面发挥作用(Mori等人，1995；Mori，1995)。在腭部融合的过程中，相对的腭架的中线上皮融合可能需要凋亡细胞的死亡(Mori等人，1994)。此外，我们还对BrdU致胎鼠肢体畸形的原因进行了研究，发现BrdU处理后的小鼠胚胎后肢芽前部多指畸形和第一趾三指畸形的形成过程中，后肢芽前部的几个基因，包括细胞凋亡相关基因、HOX基因和生长因子基因的表达发生了变化。此外，我们对一些睾丸特异基因缺陷小鼠的睾丸细胞凋亡的分析表明，在第一波精子发生过程中，粗线期细胞中的细胞凋亡水平增加(Mori等人，1997)。需要进一步的研究来明确细胞凋亡在哺乳动物形态发生过程中的意义。