Apoptsis in mammalian morphogenesis.

程序性细胞死亡是哺乳动物形态发生过程中常见的事件，在形态学上被称为细胞凋亡。哺乳动物发育肢体指间间隙的细胞死亡和哺乳动物次腭融合过程中线上皮缝的消失是形态发生程序性细胞死亡的典型例子。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起着关键作用。然而，我们的研究表明，在哺乳动物肢体和腭发育过程中，程序性细胞死亡除了消除不必要的细胞外，还起着更积极的作用。在哺乳动物肢体发育过程中，程序性细胞死亡可能在阻止额外手指的形成和减小第一手指的大小以及手指分离和关节形成方面发挥作用（Mori et al., 1995; Mori, 1995）。在腭融合过程中，为了破坏中线上皮缝或消除不能迁移或转化的不必要细胞，可能需要程序性细胞死亡，但对于腭架的初始接触或对立腭架的上皮融合可能不是必需的（Mori et al., 1994）。此外，我们报道了BrdU对胎鼠肢体畸形的形态学分析（Nakamura etal ., 1995），以及BrdU处理的小鼠胎儿在前轴多指畸形和第一趾三指畸形形成过程中后肢芽前区Hoxd-11基因转录本的表达改变（Nakamura etal ., 1996）。此外，我们在胚胎小鼠腭器官培养中开发了反义策略，用于分析形态发生机制（Naitoh等，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).