Tight Junctions during Development

Abstract

During early development, tight junction biogenesis and the differentiation of the first epithelium in the blastocyst is critical for embryonic patterning and organization. Here, we discuss the programme of exactly timed transcription, translation, and post-translational modification of specific junctional proteins that regulates the stepwise membrane assembly of tight junctions during cleavage in the mouse model. Underlying mechanisms that coordinate these processes are discussed along with newly emerging data from other mammalian species. In the mouse embryo, junction assembly follows the establishment of cell polarity at the 8-cell stage and is characterized by sequential membrane delivery of JAM-1, ZO-1α− and Rab13, cingulin and ZO-2 followed by ZO-1α+ and occludin. Tight junction assembly occurs over three developmental stages; compaction, first differentiative division and cavitation. Post-translational modification of occludin, the late expression of ZO-1α+ isoform and their intracellular colocalisation may all contribute to the rapid coordinated delivery of these two proteins to the membrane, resulting in the final sealing of the tight junction followed by blastocoel cavitation. This coordinated delivery of these two tight junction-associated proteins may therefore provide a rate limiting step for the sealing of tight junctions and regulated timing of blastocoel cavitation. Taken together, our studies in mouse, human and bovine embryos suggest that defects in the tightly controlled programming of early development may contribute to reduced embryo viability.