Cancer and Developmental Biology Laboratory, CCR, NCI-Frederick, Frederick, Maryland, USA.
Dev Dyn. 2011 May;240(5):1303-10. doi: 10.1002/dvdy.22637.
Sonic hedgehog (Shh) controls the number and type of digits formed. Using a conditional genetic approach for timed removal of Shh, we previously proposed a biphasic model of Shh function: a transient patterning phase, during which digit progenitors are specified, and an extended proliferative phase, during which expansion of progenitor pools enables digit formation. Other models favor a close integration of digit patterning and expansion, with sequential promotion to more posterior identity over time, apparently supported by some mutants with selective posterior digit loss. To further test these models, we analyzed the dynamics of Shh activity in several oligodactylous mutants with different types of digit loss. The profile of Shh activity and phenotypic outcome in these mutants supports a biphasic over an integrated temporal model. Eomesodermin expression, as an independent marker of posterior digit identity, confirmed that proper digit 4 specification requires only the transient phase of Shh activity.
声波刺猬(Shh)控制着形成的数字的数量和类型。使用条件性遗传方法定时去除 Shh,我们之前提出了 Shh 功能的双相模型:一个短暂的模式形成阶段,在此期间指定数字前体,以及一个扩展的增殖阶段,在此期间前体池的扩张使数字形成。其他模型更倾向于数字模式形成和扩张的紧密结合,随着时间的推移,逐渐向更后的身份推进,这显然得到了一些具有选择性后趾缺失的突变体的支持。为了进一步测试这些模型,我们分析了几种具有不同类型趾缺失的多指突变体中 Shh 活性的动力学。这些突变体中 Shh 活性的特征和表型结果支持一个双相模型,而不是一个整合的时间模型。Eomesodermin 表达作为后趾身份的独立标志物,证实了正确的数字 4 特异性仅需要 Shh 活性的短暂阶段。