Figure 3.

Comparative approach to discovering biological responses that promote or inhibit regeneration after spinal cord injury.

(A) Gene expression profiling of responses to SCI in non-mammalian model organisms that recover function after SCI will provide a critical step towards understanding the responses able to regulate this process in mammals. By comparing responses shared across regeneration-competent species and contrasting with those in mammals, we can predict pro-regenerative factors that are evolutionarily conserved and those that are unique to non-mammalian vertebrates. It will also allow us to predict anti-regenerative factors regulated by SCI that are evolutionarily conserved and those that are unique to mammals. (B) Ongoing and future studies using tools of genetic and pharmacologic manipulation will functionally test these predictions by applying candidate pro-regenerative factors (upper) or inhibiting candidate anti-regenerative factors (lower). Together, such experiments will identify new targets for intervention in mammalian models of axonal injury and regeneration.