Actin disruption is associated with altered YAP/TAZ-responsive transcription and reduced migration during palatal shelf elevation.

INTRODUCTION

Palatal shelf elevation requires coordinated mesenchymal remodeling, but the relationship between actin organization, mechanosensitive transcription, and mesenchymal motility remains incompletely defined. This study examined how actin disruption relates to YAP/TAZ-responsive transcription and palatal mesenchymal behavior.

METHODS

Primary mouse embryonic palatal mesenchymal cells and E13.5 palate organ cultures were treated with latrunculin A (Lat-A). Actin organization, YAP localization, wound closure, and palatal shelf orientation were assessed. GA-017, a LATS1/2 inhibitor that can activate both YAP and TAZ, was used to examine responses in the Lat-A background. RNA sequencing and reanalysis of public single-cell multiomic and spatial transcriptomic datasets characterized the associated transcriptional programs.

RESULTS

Lat-A disrupted filamentous actin, reduced wound closure, and altered YAP localization. Reduced wound closure persisted in the presence of mitomycin. GA-017 partially opposed the Lat-A-associated changes in wound closure and transcription. RNA sequencing identified 674 genes with opposite-direction changes in the Lat-A-versus-control and Lat-A-plus-GA-017-versus-Lat-A comparisons, including Ccn1, Ccn2, Ankrd1, and Amotl2. In organ culture, Lat-A was associated with reduced F-actin, YAP, CCN1, and CCN2 signals and abnormal palatal shelf orientation. Public datasets provided complementary evidence for the developmental expression and spatial overlap of YAP/TEAD-, CCN-, actin-, and migration-related programs.

DISCUSSION: These findings link actin disruption to altered LATS-sensitive YAP/TAZ-responsive transcription and reduced palatal mesenchymal wound closure during palatal elevation. CCN1 and CCN2 are candidate components of this response.