An Updated Overview on Wnt Signaling Pathways

Abstract

Growth factor signaling is required for cellular differentiation, tissue morphogenesis, and tissue homeostasis.Misregulation of intracellular signal transduction can lead to developmental defects during embryogenesis or particular diseases in the adult. One family of growth factors important for these aspects is given by the Wnt proteins. In particular, Wnts have important functions in stem cell biology, cardiac development and differentiation, angiogenesis, cardiac hypertrophy, cardiac failure, and aging. Knowledge of growth factor signaling during differentiation will allow for improvement of targeted differentiation of embryonic or adult stem cells toward functional cardiomyocytes or for understanding the basis of diseases. Our major aim here is to provide a state of the art review summarizing our present knowledge of the intracellular Wnt-mediated signaling network. In particular, we provide evidence that the subdivision into canonical and noncanonical Wnt signaling pathways solely based on the identity of Wnt ligands or Frizzled receptors is not appropriate anymore. We thereby deliver a solid base for further upcoming articles of a review series focusing on the role of Wnt proteins on different aspects of cardiovascular development and dysfunction.

Canonical and noncanonical Wnt signaling in neural stem/progenitor cells

“…Other events such as activation of ROCK have also been linked to this pathway [21]. Calcium release activates calcineurin (CNA) and Ca 2+ /calmodulin-dependent protein kinase II (CAMKII), which respectively increase expression of nuclear factor of activated Tcells (NFAT)-dependent genes and inhibit canonical Wnt signaling through nemolike kinase (NLK) [22]. This pathway is involved in cancer, inflammation and neurodegeneration [3,23].…”

Controlled levels of canonical Wnt signaling are required for neural crest migration

“…Wnts are a large family of secreted lipid-modified glycoproteins (Willert and Nusse, 2012), which can transduce signal through several different pathways including the canonical or β-catenin-dependent pathway and the non-canonical or β-catenin-independent pathways, which can be divided further into the Planar Cell Polarity (PCP) pathway and the Wnt/Ca2+ pathway (Komiya and Habas, 2008;Rao and Kühl, 2010) (Fig.1.3). Depending which pathway becomes activated Wnts are subdivided into two classes; canonical and non-canonical according to the ability to induce accumulation of β-catenin in the nucleus.…”

The Wnt pathway and the roles for its antagonists, DKKS, in angiogenesis

“…At least 19 conserved members of the Wnt family have been identified to date, most of which signal by binding to the Frizzeld (Fz) receptor. Wnts regulate a wide array of cellular and biological processes, such as cell proliferation, survival, polarity, adhesion, migration, and development of various tissues by modulating both cellular and transcriptional events (1). Wnt signaling has been found to be altered in multiple pathological conditions, including cancer, osteoporosis, and cardiovascular diseases (2)(3)(4).…”