Afadin orients cell division to position the tubule lumen in developing renal tubules.

In many types of tubules, continuity of the lumen is paramount to tubular function, yet how tubules generate lumen continuity in vivo is not known. We recently found that the F-actin-binding protein afadin is required for lumen continuity in developing renal tubules, though its mechanism of action remains unknown. Here, we demonstrate that afadin is required for lumen continuity by orienting the mitotic spindle during cell division. Using an in vitro 3D cyst model, we find that afadin localizes to the cell cortex adjacent to the spindle poles and orients the mitotic spindle. In tubules, cell division may be oriented relative to two axes: longitudinal and apical-basal. Unexpectedly, in vivo examination of early-stage developing nephron tubules reveals that cell division is not oriented in the longitudinal (or planar-polarized) axis. However, cell division is oriented perpendicular to the apical-basal axis. Absence of afadin in vivo leads to misorientation of apical-basal cell division in nephron tubules. Together, these results support a model whereby afadin determines lumen placement by directing apical-basal spindle orientation, resulting in a continuous lumen and normal tubule morphogenesis.

Complete elimination of incessant polymorphic ventricular tachycardia in an infant with MIDAS syndrome: use of endocardial mapping and radiofrequency catheter ablation.

Experience with radiofrequency catheter ablation of ventricular tachycardia (VT) in pediatric patients is limited. A 5-month-old white female infant (body weight 5.5 kg) with MIDAS syndrome who suffered from incessant polymorphic VT (ventricular rates 250 to 300 beats/min) and was unresponsive to medical treatment resulting in significantly depressed left ventricular (LV) function underwent a total of four catheter ablation procedures during a 5-month period. Each of the procedures reduced the number of morphologies and the rate of the tachycardia, but VT returned after each of the first three procedures, despite concomitant medical therapy. Activation mapping and pace mapping were used to identify the anatomic substrates, which were found at different locations at the LV septum and LV free wall. All forms of VT finally were ablated successfully. There were no significant complications. After the fourth procedure, the patient was in continuous sinus rhythm. Follow-up examination 29 months after the last procedure while the child was not taking any medication showed normal sinus rhythm and normal LV function. This report demonstrates the usefulness and safety of radiofrequency catheter ablation in an infant with polymorphic VT who was unresponsive to medical therapy.