title: Expression change in Angiopoietin-1 underlies change in relative brain size in fish.
abstract: Brain size varies substantially across the animal kingdom and is often associated with cognitive ability; however, the genetic architecture underpinning natural variation in these key traits is virtually unknown. In order to identify the genetic architecture and loci underlying variation in brain size, we analysed both coding sequence and expression for all the loci expressed in the telencephalon in replicate populations of guppies (Poecilia reticulata) artificially selected for large and small relative brain size. A single gene, Angiopoietin-1 (Ang-1), a regulator of angiogenesis and suspected driver of neural development, was differentially expressed between large- and small-brain populations. Zebra fish (Danio rerio) morphants showed that mild knock down of Ang-1 produces a small-brained phenotype that could be rescued with Ang-1 mRNA. Translation inhibition of Ang-1 resulted in smaller brains in larvae and increased expression of Notch-1, which regulates differentiation of neural stem cells. In situ analysis of newborn large- and small-brained guppies revealed matching expression patterns of Ang-1 and Notch-1 to those observed in zebrafish larvae. Taken together, our results suggest that the genetic architecture affecting brain size in our population may be surprisingly simple, and Ang-1 may be a potentially important locus in the evolution of vertebrate brain size and cognitive ability.
authors.affiliation: Neuroscience Center and Institute of Biomedicine, Anatomy, University of Helsinki, Haartmaninkatu 8, Helsinki 00290, Finland.
authors.forename: Yu-Chia
authors.initials: YC
authors.lastname: Chen
authors.affiliation: Department of Genetics, Evolution and Environment, University College London, Gower Street, London WC1E 6BT, UK.
authors.forename: Peter W
authors.initials: PW
authors.lastname: Harrison
authors.affiliation: Department of Ecology and Genetics/Animal Ecology, Uppsala University, Norbyvägen 18D, Uppsala 75236, Sweden Department of Zoology/Ethology, Stockholm University, Svante Arrhenius väg 18B, Stockholm 10691, Sweden.
authors.forename: Alexander
authors.initials: A
authors.lastname: Kotrschal
authors.affiliation: Department of Ecology and Genetics/Animal Ecology, Uppsala University, Norbyvägen 18D, Uppsala 75236, Sweden Department of Zoology/Ethology, Stockholm University, Svante Arrhenius väg 18B, Stockholm 10691, Sweden niclas.kolm@zoologi.su.se.
authors.forename: Niclas
authors.initials: N
authors.lastname: Kolm
authors.affiliation: Department of Genetics, Evolution and Environment, University College London, Gower Street, London WC1E 6BT, UK.
authors.forename: Judith E
authors.initials: JE
authors.lastname: Mank
authors.affiliation: Neuroscience Center and Institute of Biomedicine, Anatomy, University of Helsinki, Haartmaninkatu 8, Helsinki 00290, Finland.
authors.forename: Pertti
authors.initials: P
authors.lastname: Panula
mesh_terms: D000091304:Angiopoietin-Like Protein 1; D000075802:Angiopoietin-like Proteins; D042682:Angiopoietins / Q000235:genetics* / Q000378:metabolism; D000818:Animals; D001921:Brain / Q000033:anatomy & histology*; D005260:Female; D005786:Gene Expression Regulation; D055785:Gene Knockdown Techniques; D008297:Male; D011036:Poecilia / Q000033:anatomy & histology / Q000235:genetics* / Q000378:metabolism; D015027:Zebrafish / Q000033:anatomy & histology / Q000235:genetics* / Q000378:metabolism; D029961:Zebrafish Proteins / Q000235:genetics* / Q000378:metabolism
chemical_list: D000091304:Angiopoietin-Like Protein 1; D000075802:Angiopoietin-like Proteins; D042682:Angiopoietins; C504920:Angptl1 protein, zebrafish; D029961:Zebrafish Proteins
keywords: artificial selection; brain size; gene expression; knock down; neuro-transcriptome