Long noncoding RNAs regulate Wnt signaling during feather regeneration

Abstract

Long non-coding RNAs (lncRNAs) are non-protein coding transcripts that are involved in a broad range of biological processes. Here, we examine the functional role of lncRNAs in feather regeneration. RNAseq profiling of the regenerating feather blastema revealed that Wnt signaling is among the most active pathways during feather regeneration, with Wnt ligands and their inhibitors showing distinct expression patterns. Co-expression analysis identified hundreds of lncRNAs with similar expression patterns to either the Wnt ligands (the Lwnt group) or their downstream target genes (the Twnt group). Among these, we randomly picked two lncRNAs in the Lwnt group and three lncRNAs in the Twnt group to validate their expression and function. Members in the Twnt group regulated feather regeneration and axis formation, whereas members in the Lwnt group showed no obvious phenotype. Further analysis confirmed that the three Twnt group members inhibit Wnt signal transduction and, at the same time, are downstream target genes of this pathway. Our results suggest that the feather regeneration model can be utilized to systematically annotate the functions of lncRNAs in the chicken genome.

The global regulatory logic of organ regeneration: circuitry lessons from skin and its appendages

“…Their tremendous regenerative capability often leads to the concept of feedback regulation (Al-Nuaimi et al, 2010;Kunche et al, 2016;Lei & Chuong, 2018). Recent progress in studying how these organs respond to damage and their repair/regeneration responses has led to interesting discoveries: the loss of contact inhibition signalling triggers epidermal regeneration (Xie et al, 2017), the level of Shh signalling dictates HF fate choice following damage (Gao et al, 2019;Haslam et al, 2021), and epithelial-mesenchymal crosstalk between Wnt ligands and their inhibitors controls feather/hair growth and regeneration (Chu et al, 2014;Hawkshaw et al, 2018Hawkshaw et al, , 2020Lin et al, 2018). Although much remains to be discovered, we propose that feedback regulatory circuitries are of paramount significance in controlling the regeneration process, offering a mechanism to sense damage globally and determine organ fate.…”

“…Whole-genome expression analysis revealed that during feather regeneration, only Wnt signalling activity changed significantly among the major pathways (Lin et al, 2018). These include the abrupt removal of Wnt ligands after plucking, followed by their gradual re-accumulation in the feather epithelium.…”

“…This interactive crosstalk drives feather regeneration. mesenchyme, whereas the gradual accumulation of Wnt ligands during progressive regeneration of the feather epithelium slowly up-regulates their level again (Lin et al, 2018). Thus, a balance of Wnt signalling in the follicle will be restored by this reciprocal epithelial-mesenchymal crosstalk.…”

“…With recent progress, novel concepts are emerging regarding the molecular regulatory circuitries for organ regeneration from the perspective of systems biology. Specifically, here we discuss how epidermal regeneration is triggered following ionizing radiation (IR)-induced skin damage (Xie et al, 2017), how the HF/FF responds differentially to chemotherapy-and radiation therapy-induced damage (Chen et al, 2014;Xie et al, 2015;Huang et al, 2017Huang et al, , 2019Huang et al, , 2021Haslam et al, 2021), and the feedback mechanisms involved in wound-induced FF regeneration (Chu et al, 2014;Lin et al, 2018). The lessons learned from skin and its appendages may be useful in other systems.…”

RNA sequencing reveals lncRNA-mediated non-mendelian inheritance of feather growth change in chickens

“…Long non-coding RNAs (lncRNAs) are a kind of noncoding RNAs with a length of over 200 nucleotides (Fatica and Bozzoni 2014;Guttman and Rinn 2012), which are involved in a series of biological processes by regulating gene expression and modifying chromatin. For instance, lnc1589, lnc3500, or lnc7831 regulate the Wnt signaling during feather regeneration in the chicken (Lin et al 2018). In addition, lncFAM which is related to the growth in chickens regulated the expression of its target gene FAM48A via cis-expression (Li et al 2020).…”