Whitehead Institute for Biomedical Research, 9 Cambridge Center, Cambridge, MA 02142, USA.
Proc Natl Acad Sci U S A. 2009 Oct 6;106(40):17061-6. doi: 10.1073/pnas.0906823106. Epub 2009 Sep 14.
Regeneration requires specification of the identity of new tissues to be made. Whether this process relies only on intrinsic regulative properties of regenerating tissues or whether wound signaling provides input into tissue repatterning is not known. The head-versus-tail regeneration polarity decision in planarians, which requires Wnt signaling, provides a paradigm to study the process of tissue identity specification during regeneration. The Smed-wntP-1 gene is required for regeneration polarity and is expressed at the posterior pole of intact animals. Surprisingly, wntP-1 was expressed at both anterior- and posterior-facing wounds rapidly after wounding. wntP-1 expression was induced by all types of wounds examined, regardless of whether wounding prompted tail regeneration. Regeneration polarity was found to require new expression of wntP-1. Inhibition of the wntP-2 gene enhanced the polarity phenotype due to wntP-1 inhibition, with new expression of wntP-2 in regeneration occurring subsequent to expression of wntP-1 and localized only to posterior-facing wounds. New expression of wntP-2 required wound-induced wntP-1. Finally, wntP-1 and wntP-2 expression changes occurred even in the absence of neoblast stem cells, which are required for regeneration, suggesting that the role of these genes in polarity is independent of and instructive for tail formation. These data indicate that wound-induced input is involved in resetting the normal polarized features of the body axis during regeneration.
再生需要指定新组织的身份。这个过程是否只依赖于再生组织的内在调节特性,或者伤口信号是否为组织重编程提供输入尚不清楚。在涡虫中,头部与尾部的再生极性决定需要 Wnt 信号,这为研究再生过程中组织身份指定提供了一个范例。Smed-wntP-1 基因是再生极性所必需的,并且在完整动物的后极表达。令人惊讶的是,wntP-1 在受伤后很快就在前向和后向伤口处表达。wntP-1 的表达被所有类型的伤口诱导,无论伤口是否引发尾部再生。发现再生极性需要 wntP-1 的新表达。抑制 wntP-2 基因增强了由于 wntP-1 抑制引起的极性表型,wntP-2 的新表达发生在 wntP-1 之后,并且仅局限于后向伤口。wntP-2 的新表达需要伤口诱导的 wntP-1。最后,即使在不需要再生的成体干细胞存在的情况下,wntP-1 和 wntP-2 的表达变化也会发生,这表明这些基因在极性中的作用独立于并指导尾部形成。这些数据表明,伤口诱导的输入参与了在再生过程中重置身体轴的正常极化特征。