Effect of retinoic acid signaling on Ripply3 expression and pharyngeal arch morphogenesis in mouse embryos.

BACKGROUND: Pharyngeal arches (PA) are sequentially generated in an anterior-to-posterior order. Ripply3 is essential for posterior PA development in mouse embryos and its expression is sequentially activated in ectoderm and endoderm prior to formation of each PA. Since the PA phenotype of Ripply3 knockout (KO) mice is similar to that of retinoic acid (RA) signal-deficient embryos, we investigated the relationship between RA signaling and Ripply3 in mouse embryos. RESULTS: In BMS493 (pan-RAR antagonist) treated embryos, which are defective in third and fourth PA development, Ripply3 expression is decreased in the region posterior to PA2 at E9.0. This expression remains and its distribution is expanded posteriorly at E9.5. Conversely, high dose RA exposure does not apparently change its expression at E9.0 and 9.5. Knockout of retinaldehyde dehydrogenase 2 (Raldh2), which causes more severe PA defect, attenuates sequential Ripply3 expression at PA1 and reduces its expression level. EGFP reporter expression driven by a 6 kb Ripply3 promoter fragment recapitulates the endogenous Ripply3 mRNA expression during PA development in wild-type, but its distribution is expanded posteriorly in BMS493-treated and Raldh2 KO embryos. CONCLUSION: Spatio-temporal regulation of Ripply3 expression by RA signaling is indispensable for the posterior PA development in mouse.

[Massive hemorrhage during abdominal total hysterectomy in a patient with placenta percreta].

A 33-year-old pregnant woman, who had undergone three previous cesarean sections and suspected of having placenta accrete, was scheduled for artificial abortion and abdominal total hysterectomy at 15 weeks gestation because of a probable high mortality rate. The general anesthesia was induced using fentanyl, propofol, and vecuronium and maintained with sevoflurane, fentanyl, and vecuronium, in combination with epidural anesthesia using ropivacaine. During the operation, we found that the placenta had penetrated into the posterior abdominal peritoneum and bladder wall. Sudden, massive hemorrhage was encountered when attempting to separate the placenta percreta. The massive hemorrhage, up to 11,054 ml, was controlled by transfusion, infusion, and temporary clamping of the bilateral common iliac arteries. Rapid infuser LEVEL1 and autologous blood recovery systems Electa were also used. After the surgery, the patient was transferred to the intensive care unit intubated and was discharged on the 16th posteroperative day without any complications. Anesthesiologists should be prepared for massive hemorrhage in cases of abdominal total hysterectomy with suspected placenta percreta.

Identification of a link between the tumour suppressor APC and the kinesin superfamily.

The tumour suppressor gene adenomatous polyposis coli (APC) is mutated in sporadic and familial colorectal tumours. APC is involved in the proteasome-mediated degradation of beta-catenin, through its interaction with beta-catenin, GSK-3 beta and Axin. APC also interacts with the microtubule cytoskeleton and has been localized to clusters near the distal ends of microtubules at the edges of migrating epithelial cells. Moreover, in Xenopus laevis epithelial cells, APC has been shown to move along microtubules and accumulate at their growing plus ends. However, the mechanism of APC accumulation and the nature of these APC clusters remain unknown. We show here that APC interacts with the kinesin superfamily (KIF) 3A-KIF3B proteins, microtubule plus-end-directed motor proteins, through an association with the kinesin superfamily-associated protein 3 (KAP3). The interaction of APC with KAP3 was required for its accumulation in clusters, and mutant APCs derived from cancer cells were unable to accumulate efficiently in clusters. These results suggest that APC and beta-catenin are transported along microtubules by KAP3-KIF3A-KIF3B, accumulate in the tips of membrane protrusions, and may thus regulate cell migration.