09-P044 Shp2 controls retinal progenitor cell fate

The Prdm1/Blimp1 protein acts as a transcriptional repressor by recruiting co-repressors leading to direct repression and indirect activation of gene expression. Prdm1 is dynamically expressed during development and, strikingly, has been shown to control specific differentiation programs in each of the different domains studied to date. During heart formation, Prdm1 is expressed in the second heart field (SHF) that will contribute to the outflow tract (OFT) formation. In this context, Prdm1 is also expressed in the adjacent endoderm where it is required to support the growth of the mesenchymal cells of the branchial arches 2–6. As a result, Prdm1 mutant embryos display heart septation defects. In order to analyse a cell-autonomous function in the SHF, we carried out a conditional deletion of Prdm1 using two Cre lines: MesP1Cre (early cardiac mesoderm) and Mef2cCre (anterior heart field). Mesp1Cre conditional mutants die at birth and display defects in structures of the distal OFT, derived from the SHF: uneven semilunar valves, misalignment of the great arteries and aortic arch defects. Mef2cCre conditional mutants are viable, but display a retrooesophageal subclavian artery, a defect also observed in Mesp1Cre mutants. Examination of pharyngeal arch artery (PAA) remodelling demonstrates that these phenotypes are linked with a defect in the formation of the PAA4. The difference in phenotypic severity between the two Cre lines used in this study suggests that Prdm1 plays an essential early regulatory role in mesodermal progenitor cells of the SHF that contribute to morphogenesis of the arterial pole of the heart.