Signaling molecules and pattern formation during regeneration. A) A non-regenerative blastema, formed at an anterior innervated wound site, can generate pattern if treated with Shh, Fgf8 or RA. The RA-, but not Shh- and Fgf8-, induced structures have the capacity to be correctly patterned along the P/D and A/P limb axes. (B) Shh-induced ectopic limbs fail to regenerate in response to amputation, indicating a lack of positional diversity in these structures. (C) RA induced structures demonstrate regenerative capacity, indicating the establishment and stabilization of new positional identities within the RA-induced outgrowths. (Images modified, with permission, from (McCusker et al., 2014; Nacu et al., 2016; Vieira et al., 2019))