Which process occurs first during regeneration?
Regeneration timeline begins with immediate wound healing response essential to close exposed tissues, prevent infection, and establish signaling milieu. Within minutes epidermal cells migrate and spread over wound, forming wound epithelium that becomes signaling center secreting ROS, Wnt inhibitors, and growth factors. Immune cells release cytokines activating JNK, ERK, and apoptotic signals inducing wound-induced genes. Only after epithelium sealed can neoblast recruitment, blastema formation, and proliferation start; differentiation and repatterning follow later days. Failure to close wound blocks subsequent steps, highlighting wound healing temporally and mechanistically as first obligatory process preceding repatterning, differentiation, or extensive mitosis.
Ref: Gilbert, Developmental Biology, 12th ed., Chapter 19: Wound healing as earliest step preceding blastema formation.