Mammalian heart development involves an intricate sequence of morphogenetic events. Understanding how the heart is built normally informs efforts to understand and treat congenital heart defects (the most common human birth defect), but we still lack knowledge of many basic developmental processes, at both descriptive and molecular levels. For instance, the growth and expansion of the splanchnic mesoderm region of the second heart field (SpM-SHF), a tissue that contributes to both poles of the heart, is still poorly understood. Now, Jianbo Wang and colleagues address this problem, first demonstrating that mouse SpM-SHF morphogenesis is inherently polarised: as the tissue grows due to cell division, it lengthens and narrows. This convergent extension fails following loss of the PCP ligand Wnt5a, and consequently both outflow tract and atrial septation do not complete. Wnt5a is expressed in a subset of SHF progenitors that are then bi-directionally deployed to form the dorsal mesenchymal protrusion and the pulmonary trunk. The SpM-SHF contains multicellular actin cables, with those in the medial region oriented along the mediolateral axis; these medial cables specifically are disrupted in Wnt5a−/− mutants. Finally, an activated form of the PCP effector protein Daam1 is able to rescue the outflow tract and atrial septation defects of Wnt5a−/− mutants, and restore medial actin cables. This work thus suggests that PCP signalling directed by Wnt5a leads to polarised second heart field morphogenesis via regulation of the actomyosin cytoskeleton.
