Dichaete/Sox2 reawakens organogenic potential in differentiated epithelia
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Xubo Zhang Mengqi Liu Jianhui Xiang Shian Wu Jie Shen Jianhua Huang Jean-Paul Vincent Jianzhen Zhang Wei DongThis article is a preprint. Preprints have not been peer-reviewed.
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Abstract
Certain animals exhibit remarkable regenerative capacity after injury 1. Regeneration demonstrates that differentiated tissues can re-initiate organogenic program to rebuild lost structures 2. Whether this latent developmental plasticity can be broadly reawakened in vivo without injury remains unknown. Here we show that a single transcription factor, Dichaete, the Drosophila homolog of Sox2, is sufficient to induce entire wings and sporadically well-patterned eyes, antennae and leg structures from their corresponding host organs. In contrast to transdetermination, these newly formed organs consistently retain their original identity. The activation of early cell fate markers suggests that Dichaete triggers an organ-primordium competence program whose identity is specified by local positional cues. We isolated the reprogrammed progenitor cell populations and profiled the downstream factors. Genetic analysis identifies a minimal combination of three downstream mediators, Escargot, Maelstrom and Unpaired1, that largely recapitulates wing induction. Furthermore, heterologous expression of the mouse Sox2 is also sufficient to induce nascent wing discs, indicating evolutionary conservation of Dichaete/Sox2 in inducing organogenesis. Together, our results demonstrate that defined factors can unlock latent organogenic potential, inducing de novo formation of entire organs. This study opens a potential avenue for in vivo replacement of diseased or damaged organs.
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