Institute for Research in Biomedicine, Barcelona, Spain.
PLoS Biol. 2010 Dec 14;8(12):e1000566. doi: 10.1371/journal.pbio.1000566.
Coordination of growth between and within organs contributes to the generation of well-proportioned organs and functionally integrated adults. The mechanisms that help to coordinate the growth between different organs start to be unravelled. However, whether an organ is able to respond in a coordinated manner to local variations in growth caused by developmental or environmental stress and the nature of the underlying molecular mechanisms that contribute to generating well-proportioned adult organs under these circumstances remain largely unknown. By reducing the growth rates of defined territories in the developing wing primordium of Drosophila, we present evidence that the tissue responds as a whole and the adjacent cell populations decrease their growth and proliferation rates. This non-autonomous response occurs independently of where growth is affected, and it is functional all throughout development and contributes to generate well-proportioned adult structures. Strikingly, we underscore a central role of Drosophila p53 (dp53) and the apoptotic machinery in these processes. While activation of dp53 in the growth-depleted territory mediates the non-autonomous regulation of growth and proliferation rates, effector caspases have a unique role, downstream of dp53, in reducing proliferation rates in adjacent cell populations. These new findings indicate the existence of a stress response mechanism involved in the coordination of tissue growth between adjacent cell populations and that tissue size and cell cycle proliferation can be uncoupled and are independently and non-autonomously regulated by dp53.
器官之间和内部的生长协调有助于生成比例协调的器官和功能整合的成年人。帮助协调不同器官之间生长的机制开始被揭示。然而，一个器官是否能够以协调的方式对由发育或环境压力引起的局部生长变化做出反应，以及在这些情况下有助于生成比例协调的成年器官的潜在分子机制的性质，在很大程度上仍然未知。通过降低果蝇发育翅膀原基中特定区域的生长速度，我们提供了证据表明组织作为一个整体做出反应，相邻的细胞群降低其生长和增殖速度。这种非自主性反应独立于受影响的生长部位发生，并且在整个发育过程中都具有功能性，并有助于生成比例协调的成年结构。引人注目的是，我们强调了果蝇 p53（dp53）和凋亡机制在这些过程中的核心作用。虽然 dp53 在生长耗尽区域的激活介导了生长和增殖速度的非自主性调节，但效应半胱天冬酶在 dp53 下游在降低相邻细胞群的增殖速度方面具有独特的作用。这些新发现表明存在一种应激反应机制，涉及相邻细胞群之间的组织生长协调，并且组织大小和细胞周期增殖可以解耦，并且由 dp53 独立和非自主地调节。
