The study investigates the role of E-cadherin in the development of mouse preimplantation embryos. E-cadherin is a cell adhesion molecule crucial for compaction and epithelial cell layer maintenance. The researchers generated embryos homozygous for a null mutation in the E-cadherin gene by homologous recombination in embryonic stem (ES) cells. These embryos, derived from heterozygous transgenic mice, died around the time of implantation, despite undergoing compaction. At the blastocyst stage, E-cadherin-negative embryos failed to form a trophectodermal epithelium or a blastocyst cavity. This demonstrates that E-cadherin is essential for the biogenesis of an epithelium, a fundamental morphogenetic event in multicellular organisms. The study also shows that residual maternal E-cadherin can mediate compaction, but it is insufficient for further development. Additionally, E-cadherin-negative embryos exhibit reduced cell adhesion and a disorganized inner cell mass, indicating that E-cadherin is crucial for both trophectodermal and inner cell mass differentiation.The study investigates the role of E-cadherin in the development of mouse preimplantation embryos. E-cadherin is a cell adhesion molecule crucial for compaction and epithelial cell layer maintenance. The researchers generated embryos homozygous for a null mutation in the E-cadherin gene by homologous recombination in embryonic stem (ES) cells. These embryos, derived from heterozygous transgenic mice, died around the time of implantation, despite undergoing compaction. At the blastocyst stage, E-cadherin-negative embryos failed to form a trophectodermal epithelium or a blastocyst cavity. This demonstrates that E-cadherin is essential for the biogenesis of an epithelium, a fundamental morphogenetic event in multicellular organisms. The study also shows that residual maternal E-cadherin can mediate compaction, but it is insufficient for further development. Additionally, E-cadherin-negative embryos exhibit reduced cell adhesion and a disorganized inner cell mass, indicating that E-cadherin is crucial for both trophectodermal and inner cell mass differentiation.