title: The zebra finch neuropeptidome: prediction, detection and expression.
abstract: BACKGROUND
  Among songbirds, the zebra finch (Taeniopygia guttata) is an excellent model system for investigating the neural mechanisms underlying complex behaviours such as vocal communication, learning and social interactions. Neuropeptides and peptide hormones are cell-to-cell signalling molecules known to mediate similar behaviours in other animals. However, in the zebra finch, this information is limited. With the newly-released zebra finch genome as a foundation, we combined bioinformatics, mass-spectrometry (MS)-enabled peptidomics and molecular techniques to identify the complete suite of neuropeptide prohormones and final peptide products and their distributions.
  
  
  RESULTS
  Complementary bioinformatic resources were integrated to survey the zebra finch genome, identifying 70 putative prohormones. Ninety peptides derived from 24 predicted prohormones were characterized using several MS platforms; tandem MS confirmed a majority of the sequences. Most of the peptides described here were not known in the zebra finch or other avian species, although homologous prohormones exist in the chicken genome. Among the zebra finch peptides discovered were several unique vasoactive intestinal and adenylate cyclase activating polypeptide 1 peptides created by cleavage at sites previously unreported in mammalian prohormones. MS-based profiling of brain areas required for singing detected 13 peptides within one brain nucleus, HVC; in situ hybridization detected 13 of the 15 prohormone genes examined within at least one major song control nucleus. Expression mapping also identified prohormone messenger RNAs in areas associated with spatial learning and social behaviours. Based on the whole-genome analysis, 40 prohormone probes were found on a commonly used zebra finch brain microarray. Analysis of these newly annotated transcripts revealed that six prohormone probes showed altered expression after birds heard song playbacks in a paradigm of song recognition learning; we partially verify this result experimentally.
  
  
  CONCLUSIONS
  The zebra finch peptidome and prohormone complement is now characterized. Based on previous microarray results on zebra finch vocal learning and synaptic plasticity, a number of these prohormones show significant changes during learning. Interestingly, most mammalian prohormones have counterparts in the zebra finch, demonstrating that this songbird uses similar biochemical pathways for neurotransmission and hormonal regulation. These findings enhance investigation into neuropeptide-mediated mechanisms of brain function, learning and behaviour in this model.
authors.affiliation: Department of Chemistry, University of Illinois at Urbana-Champaign, Urbana, IL 61801 USA.
authors.forename: Fang
authors.initials: F
authors.lastname: Xie
authors.forename: Sarah E
authors.initials: SE
authors.lastname: London
authors.forename: Bruce R
authors.initials: BR
authors.lastname: Southey
authors.forename: Suresh P
authors.initials: SP
authors.lastname: Annangudi
authors.forename: Andinet
authors.initials: A
authors.lastname: Amare
authors.forename: Sandra L
authors.initials: SL
authors.lastname: Rodriguez-Zas
authors.forename: David F
authors.initials: DF
authors.lastname: Clayton
authors.forename: Jonathan V
authors.initials: JV
authors.lastname: Sweedler
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D019295:Computational Biology; D046369:Finches / Q000235:genetics* / Q000502:physiology; D020869:Gene Expression Profiling; D017403:In Situ Hybridization; D036341:Intercellular Signaling Peptides and Proteins / Q000235:genetics* / Q000302:isolation & purification; D007858:Learning / Q000502:physiology*; D013058:Mass Spectrometry; D008969:Molecular Sequence Data; D009479:Neuropeptides / Q000235:genetics* / Q000302:isolation & purification; D020411:Oligonucleotide Array Sequence Analysis; D036361:Peptide Hormones / Q000235:genetics* / Q000302:isolation & purification; D040901:Proteomics / Q000379:methods*
chemical_list: D036341:Intercellular Signaling Peptides and Proteins; D009479:Neuropeptides; D036361:Peptide Hormones