Our findings also provide a mechanism by which TE insertion uses the local regulatory landscape, restricted by 3D genome boundaries. We show insertion of the MusD in the neighboring but separated Lbx1 regulatory domain leads to expression in a different limb developmental population 7/

Overall, we describe how VLP production in post-implantation embryos can interfere with organ formation 6/

But how do MusD VLPs in the cell drive this phenotype? 🤔 We generated 5 mutants of the MusD sequence. Our results showed that the Gag capsid is essential to drive a phenotype, but is not sufficient to generate the severe Dactylaplasia phenotype when reverse transcription is prevented. 5/

VLPs in the apical ectodermal ridge (AER) cells of the limb are toxic: we observed DNA damage and apoptotic cell death ☠️ at the time of digit outgrowth, causing the limb phenotype observed in adult mice 4/

Using confocal and electron microscopy, we showed that MusD expression in the same cells as Fgf8 leads to the production of intracellular viral-like particles (VLPs) in the embryo 🦠 3/

TE insertions can disrupt genes or act as enhancer/alternative promoters. Here, we show that the MusD insertion does NOT affect local gene expression. Instead, it is incorporated into the Fgf8 regulatory domain and adopts its enhancers, causing its co-expression with Fgf8 2/

We used a model of TE-linked limb malformation in mice to gain insight into transposon biology during post-implantation development. A MusD element insertion upstream of the Fgf8 gene was reported to cause Dactylaplasia (Kano et al. 2009, Schwarzer & Aktas thesis dissertations) 1/