Coupling of apical-basal polarity and planar cell polarity to interpret the Wnt signaling gradient in feather development
DEVELOPMENT
Authors: Lin, Jianqiong; Yue, Zhicao
Abstract
Sensing a global directional cue to orient cell growth is crucial in tissue morphogenesis. An anterior-posterior gradient of Wnt signaling controls the helical growth of feather branches (barbs), and thus the formation of bilateral feathers. However, it remains unclear how the keratinocytes sense this gradient and orient barb growth. Here, we show that in chicken, owing to feather branching, the global Wnt gradient is subdivided into periodic barbs. Within each barb, the anterior barbule plate cells tilt before the posterior cells. The core planar cell polarity gene Prickle1 is involved, as knockdown of its expression resulted in no cell shape change and no barb tilting. Furthermore, perturbation of the Wnt gradient leads to diffusive Prickle1 expression and loss of barb orientation. Finally, the asymmetric distribution of Wnt6/Fzd10 is coordinated by the apical-basal polarity of the barbule plate keratinocytes, which is in turn regulated by the Par3/aPKC machinery. Our data elucidate a new mechanism through which the global Wnt signaling gradient is interpreted locally to construct complex spatial forms.
Wnt pathway-related gene expression in inflammatory bowel disease
DIGESTIVE DISEASES AND SCIENCES
Authors: You, Joann; Nguyen, Anthony V.; Albers, C. Gregory; Lin, Fritz; Holcombe, Randall F.
Abstract
The purpose of this study was to examine the expression of Wnt pathway-related genes in patients with ulcerative colitis (UC). RNA from colonoscopic biopsies from noninflammatory bowel disease (non-IBD) subjects and UC patients were obtained and examined with a Wnt-specific microarray for the expression of Wnt pathway-related genes. Paired samples from uninflamed and inflamed areas of the colon were obtained for the UC patients. WNT2B, WNT3A, WNT5B, WNT6, WNT7A, WNT9A, and WNT11 exhibited significantly increased expression in UC compared to non-IBD patients. Frizzled 3 (FZD3) and FZD4 exhibited significantly increased expression, and FZD1 and FZD5 exhibited significantly decreased expression in UC patients. Genes with increased expression in inflamed mucosa included DKK4, DVL2, SOX17, and COL1A1. There was no difference in the expression of a panel of Wnt target genes. The expression of inducible nitric oxide synthase (INOS) was variably influenced by inflammation. Significant differences in extracellular and cell-surface components of the Wnt pathway exist in the colonic mucosa of patients with UC compared with non-IBD patients, which may influence the strength or specificity of Wnt signaling. In inflammation, inhibitory components of the Wnt pathway exhibit increased expression, but no changes in Wnt pathway target gene expression are seen. The role and complex regulation of Sox17 and iNOS in IBD warrant further investigation.