生物电信号在调控脊椎动物附肢尺寸中的作用

所有生物体的器官和肢体大小都与身体成特定比例生长发育，且动物再生出的器官会和失去的原始器官在大小上完全相同。目前还不清楚在调控整个器官、附肢与身体的比例生长过程中协调细胞生长和组织分化的机制。目前本人实验室发现钙调磷酸酶，作为一种受钙离子浓度调节的磷酸酶，能作为分子开关调节成年斑马鱼鱼鳍的再生和发育。我们还发现，钙调磷酸酶通过调节kcnk5b（双孔钾离子通道）胞内c末端的特定丝氨酸从而调节鱼鳍尺寸，这些发现为研究控制成比例增长的尺寸信息提供了方法，包括离子介导的信号转导、翻译后修饰和位置信息的作用。为了确定尺寸信息是什么，以及kcnk5b 生物电信号如何转变成调节脊椎动物附肢的成比例生长的因子，本实验室将重点研究两个具体的方向: 1)确定kcnk5b如何被调控来控制附肢尺寸; 2)确定kcnk5b的电生理信号是如何影响shh和lef1的转录，这两个基因是两条形态发生信号通路的重要组成部分。

All organisms grow organs and appendages to specific proportions in relation to their bodies, and those animals that regenerate them do so to the exact same dimensions as the lost original structures. It remains unclear what the mechanisms are that coordinated cell growth and tissue differentiation states to scale entire organs and appendages with the body. My laboratory discovered that calcineurin, a calcium-regulated phosphatase, acts as a molecular switch that regulates proportional growth of regenerating and developing adult zebrafish fins. We also found that calcineurin regulates a two-pore K+-leak channel (Kcnk5b) at a specific serine in the cytosolic C-terminal tail to scale the fin. This discovery provides the means to study the scaling information that governs coordinated proportional growth. This includes the roles of ion-mediated signaling, post-translational modification, and positional information. To determine what the scaling information is and to determine how the Kcnk5b bioelectric signal translates into proportional growth of a vertebrate appendage, my laboratory will pursue two specific aims: 1) Define how Kcnk5b is regulated to control appendage scaling and 2) Determine how the elecrophysiological signals from Kcnk5b result in the transcription of shh and lef1, important components of two morphogen-mediated signal transduction pathways.