Wnt Signaling in Development and Disease

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.

Comparative genetic screens in human cells reveal new regulatory mechanisms in WNT signaling

“…The WNT pathway is a fundamental signaling system that plays central roles in embryonic development, regeneration and cancer (reviewed in Hoppler and Moon, 2014). During development, WNT signaling orchestrates transcriptional programs that regulate cell proliferation and survival, cell fate determination, and tissue patterning.…”

Macrophages as a Source and Recipient of Wnt Signals

“…Wnt signaling regulates many developmental processes, including cell fate decisions, migration, and the overall spatial patterning of tissues (8). It is one of a number of modular pathway “tools” in the developmental “toolkit” that drives tissue organization, where its contribution to immune biology is just emerging (9–11).…”

Role of gene polymorphisms in obesity incidence in Egypt

“…They express proteins of ~350-400 residues. Vertebrates have nineteen major Wnt gene families, with several subtypes within some classes [7]. Wntsignaling is thought to proceed through binding to frizzled family receptors of cell surface; the signal is transported by several cytoplasmic factors to β-catenin, which pass in the nucleus and triggers the transcription of genes important in development [8].…”