Final Report Summary - GEMELLI (Gene networks controlling embryonic polarity, regulation and twinning)
Higher vertebrate embryos can generate identical (monozygotic) twins when a single embryo splits into two. What mechanisms prevent this in the majority of embryos? What are the genes responsible for twinning? This project addresses this issue using a novel interdisciplinary combination of embryological, molecular and computational techniques. The project revealed that the transcription factor GATA2 specifies "anterior" identity in the embryo. GATA2 is not sufficient to account for twinning, but its anterior position, together with another gene, called Vg1 which is deployed posteriorly, are regulated by a higher level "global positioning system". The project revealed that the transcripton fator Pitx2 (also involved in specifying left-right asymmetry later in development) is a direct and essential regulator of Vg1 expression both during normal development and during twinning. It also uncovered at least 4 more genes that form part of the Global Positioning System. These studies were complemented by an in-depth analysis of how these different signals affect the behavoiur of particular cell populations in the embryo so that they start to form the embryonic body axis. In addition, the project also generated new computational tools for analysis of the regulatory landscape around genes of interest, allowing prediction of regulatory regions. These should be useful for a large variety of studies.