HISTOLOGY AND HISTOPATHOLOGY

Cellular and Molecular Biology

 

Review

Winding through the WNT pathway during cellular development and demise

F. Li1, Z.Z. Chong1 and K. Maiese1,2

1Division of Cellular and Molecular Cerebral Ischemia, Wayne State University School of Medicine, Detroit, Michigan and 2Departments of Neurology and Anatomy and Cell Biology, Center for Molecular Medicine and Genetics, Institute of Environmental Health Sciences, Wayne State University School of Medicine, Detroit, Michigan, USA

Offprint request to: Kenneth Maiese, MD, Department of Neurology, 8C-1 UHC, Wayne State University School of Medicine, 4201 St. Antoine, Detroit, MI 48201, USA. e-mail: kmaiese@med.wayne.edu


Summary. In slightly over a period of twenty years, our comprehension of the cellular and molecular mechanisms that govern the Wnt signaling pathway continue to unfold. The Wnt proteins were initially implicated in viral carcinogenesis experiments associated with mammary tumors, but since this period investigations focusing on the Wnt pathways and their transmembrane receptors termed Frizzled have been advanced to demonstrate the critical nature of Wnt for the development of a variety of cell populations as well as the potential of the Wnt pathway to avert apoptotic injury. In particular, Wnt signaling plays a significant role in both the cardiovascular and nervous systems during embryonic cell patterning, proliferation, differentiation, and orientation. Furthermore, modulation of Wnt signaling under specific cellular influences can either promote or prevent the early and late stages of apoptotic cellular injury in neurons, endothelial cells, vascular smooth muscle cells, and cardiomyocytes. A number of downstream signal transduction pathways can mediate the biological response of the Wnt proteins that include Dishevelled, ß-catenin, intracellular calcium, protein kinase C, Akt, and glycogen synthase kinase-3ß. Interestingly, these cellular cascades of the Wnt-Frizzled pathways can participate in several neurodegenerative, vascular, and cardiac disorders and may be closely integrated with the function of trophic factors. Identification of the critical elements that modulate the Wnt-Frizzled signaling pathway should continue to unlock the potential of Wnt pathway for the development of new therapeutic options against neurodegenerative and vascular diseases. Histol Histopathol 21, 103-124 (2006)

Key words: Akt, Alzheimer’s, ß-catenin, Cardiomyocytes, Dishevelled, Endothelial cells, Erythropoietin, Frizzled, GSK-3ß, Myocardial infarction, Neurons, Retinal disease, Stem cells, VEG