The Hippo Signaling Pathway Components Lats and Yap Pattern Tead4 Activity to Distinguish Mouse Trophectoderm from Inner Cell Mass

Outside cells of the preimplantation mouse embryo form the trophectoderm (TE), a process requiring the transcription factor Tead4. Here, we show that transcriptionally active Tead4 can induce Cdx2 and other trophoblast genes in parallel in embryonic stem cells. In embryos, the Tead4 coactivator protein Yap localizes to nuclei of outside cells, and modulation of Tead4 or Yap activity leads to changes in Cdx2 expression. In inside cells, Yap is phosphorylated and cytoplasmic, and this involves the Hippo signaling pathway component Lats. We propose that active Tead4 promotes TE development in outside cells, whereas Tead4 activity is suppressed in inside cells by cell contact- and Lats-mediated inhibition of nuclear Yap localization. Thus, differential signaling between inside and outside cell populations leads to changes in cell fate specification during TE formation

Osteointegration of soft tissue grafts within the bone tunnels in anterior cruciate ligament reconstruction can be enhanced

Anterior cruciate ligament reconstruction with a soft tissue autograft (hamstring autograft) has grown in popularity in the last 10 years. However, the issues of a relatively long healing time and an inferior histological healing result in terms of Sharpey-like fibers connection in soft tissue grafts are still unsolved. To obtain a promising outcome in the long run, prompt osteointegration of the tendon graft within the bone tunnel is essential. In recent decades, numerous methods have been reported to enhance osteointegration of soft tissue graft in the bone tunnel. In this article, we review the current literature in this research area, mainly focusing on strategies applied to the local bone tunnel environment. Biological strategies such as stem cell and gene transfer technology, as well as the local application of specific growth factors have been reported to yield exciting results. The use of biological bone substitute and physical stimulation also obtained promising results. Artificially engineered tissue has promise as a solution to the problem of donor site morbidity. Despite these encouraging results, the current available evidence is still experimental. Further clinical studies in terms of randomized control trial in the future should be conducted to extrapolate these basic science study findings into clinical practice. © 2009 Springer-Verlag.postprin