Apoptsis in mammalian morphogenesis.

程序性细胞死亡是哺乳动物形态发生过程中的一种常见现象，在形态上称为细胞凋亡。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，程序性细胞死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。然而，我们的研究表明，哺乳动物四肢和上颚发育中的程序性细胞死亡除了消除不必要的细胞外，还发挥着更具侵略性的作用。在哺乳动物肢体发育中，程序性细胞死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)。在腭突融合过程中，中线上皮缝可能需要程序性细胞死亡来破坏或消除不能迁移或转化的不必要细胞，但对于腭突的初始接触或相对腭突的上皮融合可能不是必需的(Mori等人，1994)。此外，我们还报道了BrdU致小鼠胚胎肢体畸形的形态分析(Nakamura et al.，1995)，以及在BrdU处理的小鼠胚胎中轴前多指和第一趾三指畸形形成过程中后肢芽前区Hoxd-11基因转录表达的变化(Nakamura et al.，1996)。此外，我们开发了用于分析形态发生机制的胎鼠腭部器官培养的反义策略(Naitoh等人，1996)。

Programd cell death is a common event during mammalian morphogenesis, which is morphologically known as apoptosis. The cell death in interdigital spaces of the 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 formation of various structures during development, programd cell death has been considered to play a key role by eliminating unnecessary cells to achieve complicated histogenesis and organogenesis. However, our studies showed that programd cell death in the mammalian limb and palate development plays more aggressive roles in addition to the elimination of unnecessary cells. In mammalian limb development, programd cell death 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 proces of palate fusion, programd cell death may be reguired for the midline epithelial seam to disrupt or for elimination of unnecessary cells which can not migrate or transform, but may not be necessary for initial contact of palatal shelves or for the epithelial fusion of opposing palatal shelves (Mori et al., 1994). In addition, we reported the morphological analysis of limb malformations induced by BrdU in fetal mice (Nakamura et al., 1995) and the altered expression of Hoxd-11 gene transcripts 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 (Nakamura et al., 1996). Moreover, we developed the antisense strategy in organ culture of fetal mouse palates for analysis of morphogenetic mechnisms (Naitoh et al., 1996).