Primary cilia function as critical sensory organelles that mediate multiple signaling pathways, including the Hedgehog (Hh) pathway, which is essential for organ patterning and morphogenesis. Disruptions in Hh signaling have been implicated in supernumerary tooth formation and molar fusion in mutant mice. Cilk1, a highly conserved serine/threonine-protein kinase localized within primary cilia, plays a critical role in ciliary transport. Loss of Cilk1 results in severe ciliopathy phenotypes, including polydactyly, edema, and cleft palate. However, the role of Cilk1 in tooth development remains unexplored. In this study, we investigated the role of Cilk1 in tooth development. Cilk1 was found to be expressed in both the epithelial and mesenchymal compartments of developing molars. Cilk1 deficiency resulted in altered ciliary dynamics, characterized by reduced frequency and increased length, accompanied by downregulation of Hh target genes, such as Ptch1 and Sostdc1, leading to the formation of diastemal supernumerary teeth. Furthermore, in Cilk1^-/-;PCS1-MRCS1^△/△ mice, which exhibit a compounded suppression of Hh signaling, we uncovered a novel phenomenon: diastemal supernumerary teeth can be larger than first molars. Based on these findings, we propose a progressive model linking Hh signaling levels to sequential changes in tooth patterning: initially inducing diastemal supernumerary teeth, then enlarging them, and ultimately leading to molar fusion. This study reveals a previously unrecognized role of Cilk1 in controlling tooth morphology via Hh signaling and highlights how Hh signaling levels shape tooth patterning in a gradient-dependent manner.
Animals ; Hedgehog Proteins/physiology* ; Mice ; Signal Transduction/physiology* ; Tooth, Supernumerary ; Molar ; Cilia/physiology* ; Odontogenesis/physiology* ; Patched-1 Receptor ; Protein Serine-Threonine Kinases/physiology* ; Mice, Knockout ; Adaptor Proteins, Signal Transducing

Objective:To clarify the anatomical characteristics and adjacent relationship of the superior segment of the inferior vena cava during laparoscopic surgery.Methods:In December 2018, two frozen and two fresh adult cadavers were dissected. The chest of the frozen cadavers was opened along the bilateral midline of the clavicle, the anterior pericardial wall was opened, and the superior vena cava and the inferior vena cava was dissected. The abdominal cavity was opened along the midline of the abdomen, the left and right hepatic lobes were turned over, the inferior vena cava and the second hilum of the posterior segment of the liver were exposed, and the hiatus of the inferior vena cava was opened and entered the pericardium.The anatomical characteristics and adjacent relationship of the superior segment of the inferior vena cava were observed, and the length of the superior segment of the inferior vena cava was measured. The fresh frozen cadaver patients underwent laparoscopic surgery.Five 12 mm trocars were placed at the side of umbilicus, right rectus abdominis about 4 cm from umbilicus, midline of abdomen about 6 cm above umbilicus, right axillary front about 2 cm below inferior edge of liver, left midline of clavicle about 2 cm below inferior edge of liver. Laparoscopic-assisted turning of the left and right hepatic lobes, exposing the posterior inferior vena cava and the second hilum of the liver, opening of the vena cava hiatus into the pericardium.The anatomical characteristics and adjacent relationship of the upper diaphragmatic segment of the inferior vena cava were observed.Results:In two autopsies, the inferior vena cava entered the chest through the cava sulcus of the liver and the phrenic foramen cava, and then through the fibrous pericardium into the right atrium. The length from the diaphragm of inferior vena cava to the right atrium was 1.67 cm, 2.57 cm. In laparoscopic operation, the diaphragm entrance of the posterior segment of the liver inferior vena cava, the second hepatic portal and the inferior vena cava could be well exposed.The diaphragm could be opened along the hole of the vena cava with a relatively non vascular anatomical layer of adipose tissue.There was a large anatomical gap between the pericardium and the right atrium, and the inferior vena cava, the superior vena cava and the right atrium could be well exposed, and the whole diaphragm could be completely and continuously exposed from the bottom to the inferior vena cava at the entrance segment of the right atrium.Conclusions:There was a relatively avascular anatomical layer beside the inferior vena cava. During laparoscopic operation, opening the diaphragm through the abdominal cavity could safely enter the pericardium and expose the inferior vena cava, the superior vena cava and the right atrium, which provides a possibility for the removal of Mayo Ⅳ grade inferior vena cava tumor thrombus through this approach.