title: Microarray analysis of a salamander hopeful monster reveals transcriptional signatures of paedomorphic brain development.
abstract: BACKGROUND
  The Mexican axolotl (Ambystoma mexicanum) is considered a hopeful monster because it exhibits an adaptive and derived mode of development - paedomorphosis - that has evolved rapidly and independently among tiger salamanders. Unlike related tiger salamanders that undergo metamorphosis, axolotls retain larval morphological traits into adulthood and thus present an adult body plan that differs dramatically from the ancestral (metamorphic) form. The basis of paedomorphic development was investigated by comparing temporal patterns of gene transcription between axolotl and tiger salamander larvae (Ambystoma tigrinum tigrinum) that typically undergo a metamorphosis.
  
  
  RESULTS
  Transcript abundances from whole brain and pituitary were estimated via microarray analysis on four different days post hatching (42, 56, 70, 84 dph) and regression modeling was used to independently identify genes that were differentially expressed as a function of time in both species. Collectively, more differentially expressed genes (DEGs) were identified as unique to the axolotl (n = 76) and tiger salamander (n = 292) than were identified as shared (n = 108). All but two of the shared DEGs exhibited the same temporal pattern of expression and the unique genes tended to show greater changes later in the larval period when tiger salamander larvae were undergoing anatomical metamorphosis. A second, complementary analysis that directly compared the expression of 1320 genes between the species identified 409 genes that differed as a function of species or the interaction between time and species. Of these 409 DEGs, 84% exhibited higher abundances in tiger salamander larvae at all sampling times.
  
  
  CONCLUSIONS
  Many of the unique tiger salamander transcriptional responses are probably associated with metamorphic biological processes. However, the axolotl also showed unique patterns of transcription early in development. In particular, the axolotl showed a genome-wide reduction in mRNA abundance across loci, including genes that regulate hypothalamic-pituitary activities. This suggests that an axolotls failure to undergo anatomical metamorphosis late in the larval period is indirectly associated with a mechanism(s) that acts earlier in development to broadly program transcription. The axolotl hopeful monster provides a model to identify mechanisms of early brain development that proximally and ultimately affect the expression of adult phenotypes.
authors.affiliation: Department of Biology and Spinal Cord and Brain Injury Research Center, University of Kentucky, Lexington, KY 40506, USA.
authors.forename: Robert B
authors.initials: RB
authors.lastname: Page
authors.forename: Meredith A
authors.initials: MA
authors.lastname: Boley
authors.forename: Jeramiah J
authors.initials: JJ
authors.lastname: Smith
authors.forename: Srikrishna
authors.initials: S
authors.lastname: Putta
authors.forename: Stephen R
authors.initials: SR
authors.lastname: Voss
mesh_terms: D000557:Ambystoma / Q000235:genetics / Q000254:growth & development; D000558:Ambystoma mexicanum / Q000235:genetics* / Q000254:growth & development*; D000818:Animals; D001921:Brain / Q000254:growth & development / Q000378:metabolism*; D055028:Comparative Genomic Hybridization; D020869:Gene Expression Profiling; D018507:Gene Expression Regulation, Developmental; D007814:Larva / Q000235:genetics / Q000254:growth & development; D008675:Metamorphosis, Biological / Q000235:genetics*; D020411:Oligonucleotide Array Sequence Analysis; D012333:RNA, Messenger / Q000032:analysis; D014158:Transcription, Genetic
chemical_list: D012333:RNA, Messenger