RECOMBINANT LIMBS AS A MODEL TO STUDY HOMEOBOX GENE-REGULATION DURING LIMB DEVELOPMENT
RECOMBINANT LIMBS AS A MODEL TO STUDY HOMEOBOX GENE-REGULATION DURING LIMB DEVELOPMENT
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DOI：
10.1006/dbio.1994.1296
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发表时间：
1994-11-01
影响因子：
2.7
通讯作者：
FALLON, JF
中科院分区：
文献类型：
--
作者：
ROS, MA;LYONS, GE;FALLON, JF
由含有分离的前翼芽中胚层细胞的外胚层外套构建的重组肢芽形成缺乏前后极性的肢状结构。通过将一小块极化区域植入重组肢体中可以恢复极性。我们使用重组肢体来研究 Msx1 和 Msx2 以及 5' Hoxd 基因在肢体发育中的表达。在重组体的制备过程中，Msx1 和 Msx2 的可检测中胚层表达丢失。当表达恢复时，无论重组体是否极化，两个基因都在顶端中胚层中以对称方式表达。 Msx1 和 Msx2 的正常前部模式从未重新建立。 Msx1 和 Msx2 在肢体模式中所起的作用目前尚不清楚。在非极化重组肢体中，5' Hoxd 基因在横跨前后轴的亚脊中胚层中顺序且均匀地表达。它们表现出嵌套的表达域，仅显示远端限制。在极化重组体中，5' Hoxd 基因以不对称、嵌套的方式逐渐表达，邻近植入的极化区域；还有一个距离植入物较远的远端中胚层区域不表达大多数 5' Hoxd 基因。这两个观察结果都与正常肢体相似。我们的结果表明，极化区域对于 5' Hoxd 基因表达的激活或维持不是必需的，但它的存在是建立正常模式所必需的。我们认为 Hoxd 基因的表达是快速生长的肢体细胞的固有特性，并且它们的表达与肢芽近远端的生长有关。我们的数据还支持极化区域以两种方式对 Hoxd 基因表达的影响。首先，短程作用负责正常的不对称表达，其次，长程作用抑制前部细胞的 5'-Hoxd 基因表达。 (C) 1994 年学术出版社
Recombinant limb buds constructed of an ectodermal jacket containing dissociated anterior wing bud mesoderm cells form limb-like structures lacking anteroposterior polarity. Polarity can be restored by implanting a small piece of polarizing region into the recombinant limb. We used recombinant limbs to study expression of Msx1 and Msx2 and 5' Hoxd genes in limb development. Detectable mesodermal expression of Msx1 and Msx2 was lost during preparation of the recombinants. When expression was restored both genes were expressed in a symmetrical fashion in the apical mesoderm whether or not the recombinant was polarized. The normal anterior pattern of Msx1 and Msx2 was never reestablished. The roles Msx1 and Msx2 play in limb patterning are at present not clear. In nonpolarized recombinant limbs the 5' Hoxd genes were sequentially and uniformly expressed in the subridge mesoderm across the anteroposterior axis. They exhibited nested domains of expression showing exclusively distal restriction. In polarized recombinants the 5' Hoxd genes were expressed progressively in an asymmetric, nested fashion adjacent to the implanted polarizing region; there was also a distal mesodermal region further from the implant that did not express the most 5' Hoxd genes. Both of these observations are similar to the normal limb. Our results demonstrate that the polarizing region is not necessary for the activation or maintenance of 5' Hoxd gene expression but that its presence is required in order for the normal pattern to be established. We propose that the expression of the Hoxd genes is an intrinsic property of rapidly growing limb cells and that their expression is related to the limb bud proximodistal outgrowth. Our data also support the influence of the polarizing region upon Hoxd gene expression in two ways. First there is a short-range action responsible for the normal asymmetric expression and second a long-range effect suppressing the expression of 5'-Hoxd genes by the anterior cells. (C) 1994 Academic Press, Inc.