Holt-oram syndrome and atrial fibrillation: opening the (T)-box.

Cardiogenesis is a complex phenomenon: its success— and ultimately life births—depends on factors acting in a combinatorial or hierarchical fashion and turning on and off gene transcription. Actually, the incidence of cardiac defects at birth is relatively high (1% to 2%), and our comprehension of these phenomena very limited. Hence, the role of transcription factors in cardiac specification and maturation has claimed increasing attention in recent years, providing a complex and evolving picture of the molecular and cellular processes involved but leaving many questions unanswered. In this issue of Circulation Research, Postma et al1 add to a growing list of regulatory factors/functions a step forward in our understanding of cardiac morphogenesis and disclosing novel features of Tbx5.