McLaughlin Margaret E, Kruger Genevieve M, Slocum Kelly L, Crowley Denise, Michaud Norman A, Huang Jennifer, Magendantz Margaret, Jacks Tyler
Department of Biology and Center for Cancer Research, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.
Proc Natl Acad Sci U S A. 2007 Feb 27;104(9):3261-6. doi: 10.1073/pnas.0700044104. Epub 2007 Feb 20.
Tissue fusion, the morphogenic process by which epithelial sheets are drawn together and sealed, has been extensively studied in Drosophila. However, there are unique features of mammalian tissue fusion that remain poorly understood. Notably, detachment and apoptosis occur at the leading front in mammals but not in invertebrates. We found that in the mouse embryo, expression of the Nf2 tumor suppressor, merlin, is dynamically regulated during tissue fusion: Nf2 expression is low at the leading front before fusion and high across the fused tissue bridge. Mosaic Nf2 mutants exhibit a global defect in tissue fusion characterized by ectopic detachment and increased detachment-induced apoptosis (anoikis). By contrast with core components of the junctional complex, we find that merlin is required specifically for the assembly but not the maintenance of the junctional complex. Our work reveals that regulation of Nf2 expression is a previously unrecognized means of controlling adhesion at the leading front, thereby ensuring successful tissue fusion.
组织融合是上皮细胞层聚集并封闭的形态发生过程，在果蝇中已得到广泛研究。然而，哺乳动物组织融合的独特特征仍知之甚少。值得注意的是，在哺乳动物中，组织融合前沿会发生细胞脱离和凋亡，而在无脊椎动物中则不会。我们发现，在小鼠胚胎中，Nf2肿瘤抑制因子merlin的表达在组织融合过程中受到动态调控：在融合前，前沿部位的Nf2表达较低，而在融合后的组织桥中表达较高。镶嵌型Nf2突变体在组织融合方面表现出全局性缺陷，其特征是异位脱离和脱离诱导的凋亡（失巢凋亡）增加。与连接复合体的核心成分不同，我们发现merlin是连接复合体组装所特需的，而非维持连接复合体所必需。我们的研究表明，Nf2表达的调控是一种此前未被认识到的控制前沿黏附的方式，从而确保组织融合成功。
