egr3 is a mechanosensitive transcription factor gene required for cardiac valve morphogenesis.

Biomechanical forces, and their molecular transducers, including key mechanosensitive transcription factor genes, such as KLF2, are required for cardiac valve morphogenesis. However, klf2 mutants fail to completely recapitulate the valveless phenotype observed under no-flow conditions. Here, we identify the transcription factor EGR3 as a conserved biomechanical force transducer critical for cardiac valve formation. We first show that egr3 null zebrafish display a complete and highly penetrant loss of valve leaflets, leading to severe blood regurgitation. Using tissue-specific loss- and gain-of-function tools, we find that during cardiac valve formation, Egr3 functions cell-autonomously in endothelial cells, and identify one of its effectors, the nuclear receptor Nr4a2b. We further find that mechanical forces up-regulate egr3/EGR3 expression in the developing zebrafish heart and in porcine valvular endothelial cells, as well as during human aortic valve remodeling. Altogether, these findings reveal that EGR3 is necessary to transduce the biomechanical cues required for zebrafish cardiac valve morphogenesis, and potentially for pathological aortic valve remodeling in humans.

Multiple pkd and piezo gene family members are required for atrioventricular valve formation.

Cardiac valves ensure unidirectional blood flow through the heart, and altering their function can result in heart failure. Flow sensing via wall shear stress and wall stretching through the action of mechanosensors can modulate cardiac valve formation. However, the identity and precise role of the key mechanosensors and their effectors remain mostly unknown. Here, we genetically dissect the role of Pkd1a and other mechanosensors in atrioventricular (AV) valve formation in zebrafish and identify a role for several pkd and piezo gene family members in this process. We show that Pkd1a, together with Pkd2, Pkd1l1, and Piezo2a, promotes AV valve elongation and cardiac morphogenesis. Mechanistically, Pkd1a, Pkd2, and Pkd1l1 all repress the expression of klf2a and klf2b, transcription factor genes implicated in AV valve development. Furthermore, we find that the calcium-dependent protein kinase Camk2g is required downstream of Pkd function to repress klf2a expression. Altogether, these data identify, and dissect the role of, several mechanosensors required for AV valve formation, thereby broadening our understanding of cardiac valvulogenesis.

Application of 3D Computed Tomography Reconstruction Images to Assess the Thickness and Dimensions of the Posterior Palatal Seal Area.

Few studies have been reported on the scientific measurements of the thickness and dimensions of the posterior palatal seal (PPS) area. The purpose of this study is to measure and analyze the thickness of palatal mucosa by using a three-dimensional (3D) model reconstructed with computed tomography (CT) images and to present objective values by identifying the PPS area. The CT images were reconstructed as a 3D model by separating the maxillary palate mucosa and teeth. Each reconstructed model was analyzed and the thickness was measured at 93 crossing points of each divided plane. The dimension of the PPS area was measured and the right and left dimensions of the PPS area were compared. The thickness of the palatal mucosa was thicker toward the posterior area. The thickness increased in the lateral direction and decreased again. In the PPS area, the mean dimension between the rearmost of anterior border and the most posterior line was 2.19 mm and the mean dimension between the forefront of anterior border and the most posterior line was 5.19 mm in the right side and 5.16 mm in the left side. The mean dimension from the center of the palate to the right most forward point was 6.85 mm, and the left was 7.36 mm. The new measurement method of palatal mucosal thickness is noninvasive, accurate, and easy to store and study, so it can be used effectively in planning and manufacturing the maxillary complete denture in the digital workflows.