Genetic reporter for live tracing fluid flow forces during cell fate segregation in mouse blastocyst development

Mechanical forces are known to be important in mammalian blastocyst formation; however, due to limited tools, specific force inputs and how they relay to first cell fate control of inner cell mass (ICM) and/or trophectoderm (TE) remain elusive. Combining in toto live imaging and various perturbation experiments, we demonstrate and measure fluid flow forces existing in the mouse blastocyst cavity and identify Klf2(Krüppel-like factor 2) as a fluid force reporter with force-responsive enhancers. Long-term live imaging and lineage reconstructions reveal that blastomeres subject to higher fluid flow forces adopt ICM cell fates. These are reinforced by internal ferrofluid-induced flow force assays. We also utilize ex vivo fluid flow force mimicking and pharmacological perturbations to confirm mechanosensing specificity. Together, we report a genetically encoded reporter for continuously monitoring fluid flow forces and cell fate decisions and provide a live imaging framework to infer force information enriched lineage landscape during development.Video abstracteyJraWQiOiI4ZjUxYWNhY2IzYjhiNjNlNzFlYmIzYWFmYTU5NmZmYyIsImFsZyI6IlJTMjU2In0.eyJzdWIiOiI2NmZiMjUzMjAyNTE2ODVkNzI2MDhlZDQ1OGI5Nzk2YSIsImtpZCI6IjhmNTFhY2FjYjNiOGI2M2U3MWViYjNhYWZhNTk2ZmZjIiwiZXhwIjoxNjk0ODE2MjEzfQ.b_UfIUybk9KSGmNo6-yCZgCAm6M-CEAXVeh_LEqkvNEJnaT7QFHKDCM1Ilcpt82b9zLlmnrGErt1KV2O86OMYhOHkP7Us1oXe2h-uBGB9wagJn0s7izpUXd8togLxZLGLoi25E5_2S841hAugQ4NJ5pQfki5K4h0qCcADT8bDbAsQ510u38eNBxZ8uvcf4Rn7XiVXftgyXCiuOHT6mVGhf3XFaWYWkkgA6BO_9gAysezT2ocStEYfH6JXtW7XEDQ6r0Du2e4Wg3JS_Nt9SUWnmQoyjW7kaFOoqj6Qzoc4qIzx0uzCpdXt3MdwuYzoIh4_zZDClJBzT7fh0ueUJstHw(mp4, (80.85 MB) Download video