DISSECTING THE ROLE OF KERATIN INTERMEDIATE FILAMENTS IN THE EARLY MAMMALIAN EMBRYO

Abstract

The cytoskeleton plays diverse roles in regulating cellular functions and coordinating tissue-scale morphogenesis. In the early mouse embryo, the actin and microtubule cytoskeletal systems regulate the formation of an implantation-ready blastocyst. Yet, the role of keratin intermediate filaments during preimplantation development is virtually unknown. Here, I established live imaging approaches to visualize keratin filament dynamics and dissect their functions within the early embryo. Keratins are initially expressed in a subset of cells of the embryo, regulated by cell-to-cell heterogeneities in the BAF chromatin remodelling complex. Unlike other polarized proteins that are redistributed during mitosis, keratins remain apically localized and asymmetrically inherited by outer daughter cells, during the asymmetric divisions segregating outer and inner cells of the embryo. There, keratins stabilize F-actin to promote apical polarization and expression of key transcription factors Yap and Cdx2 to specify the first trophectoderm cells of the embryo. My findings identify an early function for intermediate filaments during development, and reveal a model for how heterogeneities between cells can bias lineage fate via differential regulation of keratins in the mouse embryo.