Wingless: developmentally important genes that respond adversely to smoking
- Developmental Biology and Regenerative Medicine Program, Saban Research Institute, Children's Hospital Los Angeles, University of Southern California, Los Angeles, California 90027, USA
- Correspondence to Dr David Warburton, Developmental Biology and Regenerative Medicine Program, Saban Research Institute, Children's Hospital Los Angeles, University of Southern California, Los Angeles, California 90027, USA;
It has been observed by many authors that cigarette smoking results in long standing epithelial damage and interstitial inflammation within the lung. Quitting strongly reduces the risk of smoking associated lung diseases such as chronic obstructive pulmonary disease (COPD), but the underlying inflammation of the airways does not go away completely even after quitting smoking. So, a critical question for the pulmonary physician is: why is smoking cigarettes so bad for the airway lining and why are the inflammatory effects so long lasting?
Heijink et al, working with cultures of human primary bronchial epithelial cell (PBEC) biopsy specimens, now come with an intriguing new finding that cigarette smoking has significant adverse affects on certain members of the Wingless family, entraining a feed forward mechanism that increases epithelial cytokine production in response to cigarette smoke extract.1
The Wingless family comprises an important class of developmentally critical signalling ligands that conduct signals from the cell surface through the cytoplasm to the nucleus, where they activate coordinated sets of genes. These genes in turn regulate cell–cell communication in the embryonic through the adult stages of human and animal development and continue to be very important in airway epithelial differentiation as well as during airway epithelial healing (see Warburton et al2 for a recent review).
The colourful name Wingless was coined to describe the loss of function phenotype of fruit flies that lack this gene (they have no wings). Fruit fly geneticists, being somewhat perverse, always delight in giving active voice picaresque names to their loss of function phenotypes. Thus, conversely, signalling by Wingless ligands actually induces the correct differentiation of epithelial cells that form the wing structures in flies and this basic developmental function is conserved, but has been adapted during evolution all the way up …