Frizzled Receptors in Development and Disease

Curr Top Dev Biol. 2016;117:113-39. doi: 10.1016/bs.ctdb.2015.11.028. Epub 2016 Jan 27.

Abstract

Frizzled proteins are the principal receptors for the Wnt family of ligands. They mediate canonical Wnt signaling together with Lrp5 and Lrp6 coreceptors. In conjunction with Celsr, Vangl, and a small number of additional membrane and membrane-associated proteins, they also play a central role in tissue polarity/planar cell polarity (PCP) signaling. Targeted mutations in 9 of the 10 mammalian Frizzled genes have revealed their roles in an extraordinarily diverse set of developmental and homeostatic processes, including morphogenetic movements responsible for palate, ventricular septum, ocular furrow, and neural tube closure; survival of thalamic neurons; bone formation; central nervous system (CNS) angiogenesis and blood-brain barrier formation and maintenance; and a wide variety of processes that orient subcellular, cellular, and multicellular structures relative to the body axes. The last group likely reflects the mammalian equivalent of tissue polarity/PCP signaling, as defined in Drosophila, and it includes CNS axon guidance, hair follicle and tongue papilla orientation, and inner ear sensory hair bundle orientation. Frizzled receptors are ubiquitous among multicellular animals and, with other signaling molecules, they very likely evolved to permit the development of the complex tissue architectures that provide multicellular animals with their enormous selective advantage.

Keywords: Angiogenesis; Axon guidance; Blood–brain barrier; Hair follicles; Planar cell polarity; Tissue polarity.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Cell Polarity*
  • Disease*
  • Frizzled Receptors / metabolism*
  • Hair Follicle / cytology*
  • Hair Follicle / metabolism
  • Humans
  • Neurons / cytology*
  • Neurons / metabolism
  • Signal Transduction

Substances

  • Frizzled Receptors