GSE111098
ATAC-Seq of chicken embryonic metatarsal skin treated with RCAS-CTNNB1, RCAS-GFP, and retinoic acid
The molecular mechanism controlling regional specific skin appendage phenotypes is a fundamental question that remains unresolved. We recently identified feather and scale primordium associated genes and with functional studies, proposed five major more modules are involved in scale-to-feather conversion and their integration is essential to form today's feathers. Yet, how the molecular networks are wired and integrated at the genomic level is still unknown. Here, we combine classical recombination experiments and systems biology technology to explore the molecular mechanism controlling cell fate specification. In the chimeric explant, dermal fate is more stable, while epidermal fate is reprogrammed to be similar to the original appendage type of the mesenchyme. We analyze the transcriptome changes in both scale-to-feather and feather-to-scale transition in the epidermis. We found a highly interconnected regulatory gene network controlling skin appendage types. These gene networks are organized around two molecular hubs, ß-catenin and retinoic acid (RA), which can bind to regulatory elements controlling downstream gene expression, leading to scale or feather fates. ATAC sequencing analyses revealed about 1000 altered chromatin opening sites, and they are distributed around. When a key gene is perturbed, many other co-expressed genes in the same module also will be influenced. These findings suggest that these feather / scale fate specification genes form an interconnected network, and rewiring of the gene network can lead to changes of appendage phenotypes. This work shows the key hub positions of Beta catenin and retinoic acid signaling in the hierarchy of the scale / feather fate specification gene networks, opening up new possibilities to understand the control switches of multi-component organ phenotypes. Overall design: Chicken E12 metatarsal skin treated with RCAS-CTNNB1, RCAS-GFP, and retinoic acid