SOX11 and SOX4 drive the reactivation of an embryonic gene program during murine wound repair.

Qi Miao, Matthew C Hill, Fengju Chen, Qianxing Mo, Amy T Ku, Carlos Ramos, Elisabeth Sock, Véronique Lefebvre, Hoang Nguyen

Nature communications 2019 Sep 06

filter terms:

Tissue injury induces changes in cellular identity, but the underlying molecular mechanisms remain obscure. Here, we show that upon damage in a mouse model, epidermal cells at the wound edge convert to an embryonic-like state, altering particularly the cytoskeletal/extracellular matrix (ECM) components and differentiation program. We show that SOX11 and its closest relative SOX4 dictate embryonic epidermal state, regulating genes involved in epidermal development as well as cytoskeletal/ECM organization. Correspondingly, postnatal induction of SOX11 represses epidermal terminal differentiation while deficiency of Sox11 and Sox4 accelerates differentiation and dramatically impairs cell motility and re-epithelialization. Amongst the embryonic genes reactivated at the wound edge, we identify fascin actin-bundling protein 1 (FSCN1) as a critical direct target of SOX11 and SOX4 regulating cell migration. Our study identifies the reactivated embryonic gene program during wound repair and demonstrates that SOX11 and SOX4 play a central role in this process.

Citation

Qi Miao, Matthew C Hill, Fengju Chen, Qianxing Mo, Amy T Ku, Carlos Ramos, Elisabeth Sock, Véronique Lefebvre, Hoang Nguyen. SOX11 and SOX4 drive the reactivation of an embryonic gene program during murine wound repair. Nature communications. 2019 Sep 06;10(1):4042