Effect of depletion of Isl1 on gene expression at 8.75 days of embryo development
The transcription factor Isl1 is expressed in the progenitors of the Ex-Mes and allantois, however its role in the placentation remains unclear. Our studies showed that deletion of Isl1 causes defects in allantois growth, chorioallantoic fusion and placenta vessel morphogenesis. RNA-seq analyses have revealed that Isl1 regulates the expression of genes important for Ex-Mes multipotency, differentiation and diversification. Isl1 promotes allantoic endothelial but inhibits mesenchymal cell differentiation. Isl1 plays an important role in regulating multiple genetic and epigenetic pathways of vascular morphogenesis. Allantoic signals regulated by Isl1 in turn mediate the inductive interactions between the allantois and chorion critical for chorionic epithelium differentiation, villous formation, and labyrinth angiogenesis. In conclusion, our study provides an integrated insight into the mechanisms underlying placental lineage differentiation, diversification, and vascular formation, highlighting the necessity of Isl1 for early placenta morphogenesis. Our study suggests the potential utility of Isl1 in regenerative medicine application using the stem cells derived from the placenta, umbilical cord and amnionic membrane. Overall design: To understand the role of Isl1 in the inductive interactions between the allantois and chorion epithelium during chorioallantoic fusion and labyrinth formation. We generated Isl1 knock-out mice (Isl1 Cre+/-; Isletf/+) with Black Swiss background through crossed Isl1 Cre+/- females with Isl1f/+ males. Then we performed RNA-seq analysis of the feto-placentas and associated allantoises at E8.75 with Rosa-tdTomato background in order to trace Cre lineage.Comparative gene expression profiling analysis of RNA-seq data for control and Isl1-null (mut) mice littermates of the feto-placentas and associated allantoises tissue.