Department of Reconstructive Sciences, University of Connecticut Health Center, Farmington, Connecticut, USA.
Dev Dyn. 2011 May;240(5):1289-302. doi: 10.1002/dvdy.22628. Epub 2011 Apr 4.
Sonic hedgehog (Shh) signaling in the limb plays a central role in coordination of limb patterning and outgrowth. Shh expression in the limb is limited to the cells of the zone of polarizing activity (ZPA), located in posterior limb bud mesoderm. Shh is not expressed by limb ectoderm or apical ectodermal ridge (AER), but recent studies suggest a role for AER-Shh signaling in limb patterning. Here, we have examined the effects of activation of Shh signaling in the AER. We find that targeted expression of Shh in the AER activates constitutive Shh signaling throughout the AER and subjacent limb mesoderm, and causes a range of limb patterning defects with progressive severity from mild polydactyly, to polysyndactyly with proximal defects, to severe oligodactyly with phocomelia and partial limb ventralization. Our studies emphasize the importance of control of the timing, level and location of Shh pathway signaling for limb anterior-posterior, proximal-distal, and dorsal-ventral patterning.
sonic 刺猬（Shh）信号在肢体中发挥着协调肢体模式和生长的核心作用。Shh 在肢体中的表达仅限于位于后肢芽中胚层的极性活动区（ZPA）的细胞。Shh 不表达于肢体外胚层或顶端外胚层嵴（AER），但最近的研究表明 AER-Shh 信号在肢体模式形成中具有作用。在这里，我们研究了激活 AER 中的 Shh 信号的影响。我们发现，在 AER 中靶向表达 Shh 会激活整个 AER 和下方的肢体中胚层中的组成型 Shh 信号，导致一系列肢体模式缺陷，严重程度从轻度多指畸形到近端缺陷的多指并指畸形，再到严重的少指畸形伴有蹼状和部分肢体腹侧化。我们的研究强调了控制 Shh 通路信号的时间、水平和位置对于肢体前后、近端-远端和背-腹模式形成的重要性。
