Wnt5a and Wnt11 are essential for second heart field progenitor development
ABSTRACT Wnt/β-catenin has a biphasic effect on cardiogenesis, promoting the induction of cardiac progenitors but later inhibiting their differentiation. Second heart field progenitors and expression of the second heart field transcription factor Islet1 are inhibited by the loss of β-catenin, indicating that Wnt/β-catenin signaling is necessary for second heart field development. However, expressing a constitutively active β-catenin with Islet1-Cre also inhibits endogenous Islet1 expression, reflecting the inhibitory effect of prolonged Wnt/β-catenin signaling on second heart field development. We show that two non-canonical Wnt ligands, Wnt5a and Wnt11, are co-required to regulate second heart field development in mice. Loss of Wnt5a and Wnt11 leads to a dramatic loss of second heart field progenitors in the developing heart. Importantly, this loss of Wnt5a and Wnt11 is accompanied by an increase in Wnt/β-catenin signaling, and ectopic Wnt5a/Wnt11 inhibits β-catenin signaling and promotes cardiac progenitor development in differentiating embryonic stem cells. These data show that Wnt5a and Wnt11 are essential regulators of the response of second heart field progenitors to Wnt/β-catenin signaling and that they act by restraining Wnt/β-catenin signaling during cardiac development.
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ABSTRACT: Mammalian heart formation is a complex morphogenetic event that depends on the correct temporal and spatial contribution of distinct cell sources. During cardiac formation, cellular specification, differentiation, and rearrangement are tightly regulated by an intricate signaling network. Over the last years, many aspects of this network have been uncovered not only due to advances in cardiac development comprehension but also due to the use of embryonic stem cells (ESCs) in vitro model system. Additionally, several of these pathways have been shown to be functional or reactivated in the setting of cardiac disease. Knowledge withdrawn from studying heart development, ESCs differentiation, and cardiac pathophysiology may be helpful to envisage new strategies for improved cardiac repair/regeneration. In this review, we provide a comparative synopsis of the major signaling pathways required for cardiac lineage commitment in the embryo and murine ESCs. The involvement and possible reactivation of these pathways following heart injury and their role in tissue recovery will also be discussed.BioMed Research International 04/2014; 2014:679168. DOI:10.1155/2014/679168 · 2.71 Impact Factor
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ABSTRACT: Planar cell polarity (PCP), a process controlling coordinated, uniformly polarized cellular behaviors in a field of cells, has been identified to be critically required for many fundamental developmental processes. However, a global directional cue that establishes PCP in a three-dimensional tissue or organ with respect to the body axes remains elusive. In vertebrate, while Wnt-secreted signaling molecules have been implicated in regulating PCP in a β-catenin-independent manner, whether they function permissively or act as a global cue to convey directional information is not clearly defined. In addition, the underlying molecular mechanism by which Wnt signal is transduced to core PCP proteins is largely unknown. In this chapter, I review the roles of Wnt signaling in regulating PCP during vertebrate development and update our knowledge of its regulatory mechanism.Current Topics in Developmental Biology 01/2012; 101C:263-295. DOI:10.1016/B978-0-12-394592-1.00008-9 · 4.21 Impact Factor
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ABSTRACT: From the 1920s, early cardiac development has been studied in chick and, later, in mouse embryos in order to understand the first cell fate decisions that drive specification and determination of the endocardium, myocardium, and epicardium. More recently, mouse and human embryonic stem cells (ESCs) have demonstrated faithful recapitulation of early cardiogenesis and have contributed significantly to this research over the past few decades. Derived almost 15 years ago, human ESCs have provided a unique developmental model for understanding the genetic and epigenetic regulation of early human cardiogenesis. Here, we review the biological concepts underlying cell fate decisions during early cardiogenesis in model organisms and ESCs. We draw upon both pioneering and recent studies and highlight the continued role for in vitro stem cells in cardiac developmental biology.Cardiovascular Research 08/2012; 96(3). DOI:10.1093/cvr/cvs270 · 5.81 Impact Factor