Although mutations in the SCRIB gene lead to multiple morphological organ defects in vertebrates, the molecular pathway linking SCRIB to organ shape anomalies remains elusive. Here, we study the impact of SCRIB-targeted gene mutations during the formation of the gut epithelium in an organ-on-chip model. We show that SCRIB KO gut-like epithelia are flatter with reduced exposed surface area. Cell differentiation on filters further shows that SCRIB plays a critical role in the control of apical cell shape, as well as in the basoapical polarization of myosin light chain localization and activity. Finally, we show that SCRIB serves as a molecular scaffold for SHROOM2/4 and ROCK1 and identify an evolutionary conserved SHROOM binding site in the SCRIB carboxy-terminal that is required for SCRIB function in the control of apical cell shape. Our results demonstrate that SCRIB plays a key role in epithelial morphogenesis by controlling the epithelial apical contractility during cell differentiation.
SCRIB controls apical contractility during epithelial differentiation
Disclosures: The authors declare no competing interests exist.
Batiste Boëda, Vincent Michel, Raphael Etournay, Patrick England, Stéphane Rigaud, Héloïse Mary, Samy Gobaa, Sandrine Etienne-Manneville; SCRIB controls apical contractility during epithelial differentiation. J Cell Biol 4 December 2023; 222 (12): e202211113. doi: https://doi.org/10.1083/jcb.202211113
Download citation file: