人的肢芽发育过程是一种图式发育过程,Shh作为极性活化区的一个重要形态发生蛋白质,在肢芽发育过程中起着关键性作用。大量实验证据表明,Shh的胆固醇修饰可影响Shh的扩散进而调节第二指的发生,Shh表达后不经扩散直接作用于3~5指调节其发生,Shh不会在第一指发生的位置出现。Shh和其它蛋白质(包括Gli蛋白质家族,FGF蛋白质家族,Gremlin骨来蛋白等)相互作用,共同调节指的发育。该过程中,蛋白质相互作用可形成FGF/Shh正反馈回路和FGF/Gremlin负反馈回路。
The process of human limb bud development is patterning process, Shh protein plays a key role as a morphogen of ZPA during the development of the limb bud. Cholesterol modification of Shh affects its diffusion to regulate digit 2 forming. After Shh expression, it affects digit 3 to digit 5 directly to regulate their forming without diffusion. However, digit 1 doesn't need Shh in its development. Shh and other proteins(contain Gli family, Fgf family, Gremlin and so on) act with each other to form Fgf/Shh positive feedback loop and Fgf/Gremlin negative feedback loop, regulating the digital development.