Metamorphosis and the regenerative capacity of spinal cord axons in Xenopus laevis.
Throughout the vertebrate subphylum, the regenerative potential of central nervous system axons is greatest in embryonic stages and declines as development progresses. For example, Xenopus laevis can functionally recover from complete transection of the spinal cord as a tadpole but is unable to do so after metamorphosing into a frog. Neurons of the reticular formation and raphe nucleus are among those that regenerate axons most reliably in tadpole and that lose this ability after metamorphosis. To identify molecular factors associated with the success and failure of spinal cord axon regeneration, we pharmacologically manipulated thyroid hormone (TH) levels using methimazole or triiodothyronine, to either keep tadpoles in a permanently larval state or induce precocious metamorphosis, respectively. Following complete spinal cord transection, serotonergic axons crossed the lesion site and tadpole swimming ability was restored when metamorphosis was inhibited, but these events failed to occur when metamorphosis was prematurely induced. Thus, the metamorphic events controlled by TH led directly to the loss of regenerative potential. Microarray analysis identified changes in hindbrain gene expression that accompanied regeneration-permissive and -inhibitory conditions, including many genes in the permissive condition that have been previously associated with axon outgrowth and neuroprotection. These data demonstrate that changes in gene expression occur within regenerating neurons in response to axotomy under regeneration-permissive conditions in which normal development has been suspended, and they identify candidate genes for future studies of how central nervous system axons can successfully regenerate in some vertebrates.
Department of Biological Sciences, University at Albany, State University of New York, Albany, NY 12222, USA.
Kurt M
KM
Gibbs
Sridar V
SV
Chittur
Ben G
BG
Szaro
D000818:Animals; D013956:Antithyroid Agents / Q000494:pharmacology; D001369:Axons / Q000187:drug effects / Q000473:pathology / Q000502:physiology*; D001522:Behavior, Animal / Q000502:physiology; D002465:Cell Movement / Q000502:physiology; D020869:Gene Expression Profiling; D008675:Metamorphosis, Biological / Q000187:drug effects / Q000502:physiology*; D008713:Methimazole / Q000494:pharmacology; D046228:Microarray Analysis; D020127:Recovery of Function; D012249:Rhombencephalon / Q000033:anatomy & histology / Q000502:physiology; D013116:Spinal Cord / Q000166:cytology* / Q000187:drug effects / Q000473:pathology; D013119:Spinal Cord Injuries / Q000378:metabolism; D058630:Spinal Cord Regeneration / Q000187:drug effects / Q000502:physiology*; D013963:Thyroid Hormones / Q000378:metabolism; D014284:Triiodothyronine / Q000494:pharmacology; D029867:Xenopus Proteins / Q000235:genetics / Q000378:metabolism; D014982:Xenopus laevis / Q000033:anatomy & histology / Q000254:growth & development* / Q000378:metabolism
D013956:Antithyroid Agents; D013963:Thyroid Hormones; D029867:Xenopus Proteins; D014284:Triiodothyronine; D008713:Methimazole