BMP/SMAD signaling regulates the cell behaviors that drive the initial dorsal-specific regional morphogenesis of the otocyst.

During development of the otocyst, regional morphogenesis establishes a dorsal vestibular chamber and a ventral auditory chamber, which collectively constitute the membranous labyrinth of the inner ear. We identified the earliest morphogenetic event heralding the formation of the vestibular chamber, a rapid thinning and expansion of the dorsolateral wall of the otocyst, and showed that this process is generated by changes in otocyst cell shape from columnar to squamous, as opposed to changes in other cell behaviors, such as localized changes in cell proliferation or cell death. Moreover, we showed that thinning and expansion of the dorsolateral otocyst is regulated by BMP/SMAD signaling, which is both sufficient and necessary for localized thinning and expansion. Finally, we showed that BMP/SMAD signaling causes fragmentation of E-cadherin in the dorsolateral otocyst, occurring concomitantly with cell shape change, suggesting that BMP/SMAD signaling regulates cell-cell adhesion during the initial morphogenesis of the otocyst epithelium. Collectively, our results show that BMP signaling via SMADs regulates the cell behaviors that drive the initial dorsal-specific morphogenesis of the otocyst, providing new information about how regional morphogenesis of a complex organ rudiment, the developing membranous labyrinth, is initiated.