Wnt signaling in development and disease

Yingzi Yang

doi:10.1186/2045-3701-2-14

Abstract

Cell signaling mediated by morphogens is essential to coordinate growth and patterning, two key processes that govern the formation of a complex multi-cellular organism. During growth and patterning, cells are specified by both quantitative and directional information. While quantitative information regulates cell proliferation and differentiation, directional information is conveyed in the form of cell polarities instructed by local and global cues. Major morphogens like Wnts play critical roles in embryonic development and they are also important in maintaining tissue homeostasis. Abnormal regulation of these signaling events leads to a diverse array of devastating diseases including cancer. Wnts transduce their signals through several distinct pathways and they regulate vertebrate embryonic development by providing both quantitative and directional information. Here, taking the developing skeletal system as an example, we review our work on Wnt signaling pathways in various aspects of development. We focus particularly on our most recent findings that showed that in vertebrates, Wnt5a acts as a global cue to establishing planar cell polarity (PCP). Our work suggests that Wnt morphogens regulate development by integrating quantitative and directional information. Our work also provides important insights in disease like Robinow syndrome, brachydactyly type B1 (BDB1) and spina bifida, which can be caused by human mutations in the Wnt/PCP signaling pathway.

Highlights

Cell signaling mediated by morphogens is essential to coordinate growth and patterning, two key processes that govern the formation of a complex multi-cellular organism
Robinow syndrome and Brachydactyly Type B1 that are characterized by shortened skeletal elements are caused by mutations in the Wnt/planar cell polarity pathway components [8,9,10,11]
When Wnts bind to their receptors Frizzleds and Lrp5 or Lrp6, Lrp5/6 are phosphorylated and Dishevelled is activated, which lead to inactivation of the β-catenin “destruction complex” or disassembly of the β-catenin “destruction complex” such that β-catenin phosphorylation is reduced and stabilized

Summary

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39. Wolpert L

47. Strutt D

Findings

50. Axelrod JD